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Drug target identification and lead optimization of hit compound candidates for orphan diseases | Image Credit: © HYUNGKEUN -stock.adobe.com

An estimated 300 million people worldwide are affected by more than 7000 rare diseases (1). The vast majority of these conditions lack an approved therapy. Orphan drugs, in the United States, are defined as having a target population of fewer than 200,000 patients, with comparable threshold elsewhere (2). While the unmet needs are profound, the rarity of these conditions creates a high-stakes environment for orphan drug development, one which comes with built-in restrictions: limited patient populations, small batch sizes, and a scarcity of development data.

Regulatory help and hurdles

To energize the challenging landscape of orphan drug development, regulatory incentives, such as the Orphan Drug Act in the US, have helped encourage a wave of agile new sponsors. Smaller sponsors, often without in-house manufacturing or regulatory infrastructure, must navigate the inherent challenges of orphan drug development alongside the high bar of regulatory standards for quality and safety.

While expedited pathways, such as FDA’s Breakthrough Therapy and the European Medicines Agency’s (EMA) PRIME designations, can accelerate review, they do not lessen the fundamental expectations for product quality, safety, and manufacturing process robustness. Regulators require sponsors to meet the same International Council for Harmonisation (ICH) guidelines for pharmaceutical development (3), quality risk management (4), and drug substance development (5).

CMC challenges

Ensuring a drug’s quality, safety, and purity with meticulous chemistry, manufacturing and controls (CMC) is what transforms discoveries into tangible medicine. However, CMC in the orphan drug space is not a straightforward task. The same factors that define rare diseases—scarcity and urgency—create unique technical and operational challenges that can easily disrupt a program’s momentum.

In this environment, sponsors and patients often cannot afford the lost time and resources of backward steps. Success requires a zero-waste approach, where every resource, every batch, and every minute is optimized. This article uses anonymized examples to highlight how to navigate seven common CMC problems, offering a guide for maintaining development momentum and avoiding costly mistakes.

Problem 1: underestimating early-phase CMC

Non-optimized processes and temporary formulations may accelerate first-in-human milestones but can lead to expensive and time-consuming remedial work. Sponsors who use non-optimized processes, minimal characterization, and temporary formulations risk compromising a product’s long-term usability and scalability.

Example 1: one gene therapy sponsor’s use of research-grade plasmid DNA and non-GMP adeno-associated virus (AAV) vectors in early trials resulted in a lack of comparability data. This prompted regulators to question the integrity of the clinical data, forcing the sponsor to repeat toxicology studies and causing a significant delay.

Example 2: a small-molecule drug sponsor learned this lesson when its early solution formulation exhibited recrystallization during stability testing. The sponsor had not performed polymorph screening or excipient compatibility studies upfront, and the resulting reformulation introduced new impurities that required extensive bridging work, further delaying the program.

Solution: start with the end in mind

A successful program must begin with a CMC strategy that anticipates late-stage and commercial requirements. For gene therapy, this means using a manufacturing process that can be scaled up to good manufacturing practice (GMP) standards from the start. As outlined in FDA guidance on CMC information for human gene therapy, the quality of starting materials is a key concern (6). When this foresight is neglected, it can lead to a critical disconnect between early and pivotal trial data, forcing sponsors to repeat toxicology studies or re-evaluate product integrity.

Problem 2: analytical blind spots

Ongoing patient safety and efficacy rely on robust quality control. If the analytical methods used to assess a product are flawed, incomplete, or poorly validated, it sets the stage for significant downstream complications.

Example 1: a cell and gene therapy program faced a major problem when a critical potency assay lacked reproducibility. The sponsor had failed to establish a proper reference standard, and as a result, the assay failed during a key comparability test, forcing regulators to request a new method and additional clinical data.

Example 2: a small-molecule program faced a major challenge when its ultraviolet (UV)-based high-performance liquid chromatograph (HPLC) method failed to resolve a critical degradant that formed under long-term storage conditions. By the time the issue was discovered, several clinical batches had been released using a method that was not stability-indicating, raising serious questions about product integrity.

Solution: invest in a robust analytical framework

Investing in a robust analytical framework upfront prevents downstream issues. For complex modalities, this is even more critical. Journal articles on the manufacturing of gene and cell therapies highlight that the complexities of these products can lead to challenges with quality control assays (7). Analytical methods must be sufficiently robust to ensure product quality and detect degradants over a product’s shelf life.

Problem 3: taking short-cuts to control strategies

Generic or poorly justified specifications fail to instill confidence in product quality. While orphan drug programs often deal with a low number of batches, they must still demonstrate an adequate control strategy to ensure safety and efficacy. The risk of failure leads to significant regulatory hurdles as regulators scrutinize a product’s specifications as the foundation of its quality.

Example 1: a biologic program applied generic specifications from a different product type. Regulators challenged the assumptions, pointing out that the product’s degradation pathways were fundamentally different. This oversight required the sponsor to perform additional characterization and caused a several-month delay.

Example 2: in the small-molecule space, an uncharacterized impurity approached a regulatory threshold, but the sponsor had not performed a toxicological assessment. FDA requested a full evaluation, and progress stalled until the required data could be produced.

Solution: build a scientifically sound strategy

Control strategies must be product-specific, risk-based, and supported by a strong scientific rationale. A lack of process knowledge is often the root cause of issues, as noted in ICH Q11 (5). Establishing a well-defined control strategy from the beginning enables regulators to assess a product on its own merits, preventing costly delays.

Problem 4: change without big-picture visibility

Changes, even positive improvements, must be managed carefully. A seemingly minor change in formulation, process, or site can trigger unintended consequences and raise regulatory concerns if it is not supported by robust comparability data.

Example 1: in one biologics program, a purification change introduced to improve yield unintentionally affected the product’s glycosylation pattern. Because the change had not been thoroughly studied and the assays lacked sensitivity, regulators required the sponsor to generate new clinical bridging data, postponing the drug’s approval.

Example 2: a sponsor introduced a new polymorph to improve manufacturability but did not adequately characterize its impact on dissolution or bioavailability. Without an in vitro-in vivo correlation to justify the change, regulators requested additional pharmacokinetic data, resulting in a significant delay.

Solution: proactively manage the product lifecycle

Change is inevitable, but it must be managed with a proactive approach and a well-defined comparability protocol to maintain development momentum. By anticipating and planning for these changes, sponsors can prevent surprises and keep their program on track. European regulatory agencies, such as the EMA, provide specific guidance on the quality documentation required for biological products (8).

Problem 5: surprises of scale

Scaling up is an exciting stage of development, but minimizing issues requires a deep understanding of how new equipment and different process dynamics can impact a product. Without this foresight, the transition from lab to clinical or commercial scale can be more costly than it is a cause for celebration.

Example 1: in one viral vector program, a change in chromatography resin during scale-up unexpectedly altered the ratio of empty to full capsids. Because the sponsor lacked sufficiently sensitive release assays, they only discovered the issue after the clinical material failed potency testing.

Example 2: a small-molecule program experienced an undesirable change in its impurity profile during scale-up crystallization. The increase in mixing speeds and thermal gradients introduced new stress points, and the new impurity required a toxicology reassessment and repeat validation.

Solution: design for scalability from the outset

Minimizing scale-up issues requires a deep understanding of how new equipment and different process dynamics can impact a product. The need for a life-cycle approach to process validation is a well-established principle in the industry, as detailed in both Parenteral Drug Association (PDA) technical reports and EMA guidelines (9, 10).

Problem 6: precarious supply chains

For many orphan drug programs, a single vendor for a critical raw material or intermediate represents a weak link in the supply chain. While this reliance can be manageable in early development, it creates a serious point of failure as a program scales toward regulatory approval.

Example 1: in one gene therapy program, the sponsor’s single-source plasmid supplier lost its GMP certification, halting vector production. Without a qualified backup, the sponsor faced a six-month delay while it had to revalidate a new supply chain.

Example 2: A small-molecule program encountered a similar issue when its supplier of a specialized intermediate discontinued the product line. The sponsor had not developed a backup plan, so regulatory filings could not proceed until a new material source was requalified.

Solution: mitigate single-source risk

Sponsors must identify and mitigate these risks early in development by establishing dual sourcing where possible and qualifying alternate vendors. This strategic foresight provides a critical layer of resilience against unforeseen disruptions.

Problem 7: documentation gaps

Even with brilliant scientific breakthroughs, inconsistencies raise questions. Documentation could be considered a regulatory product pitch; inconsistencies, gaps, or ambiguity undermine even the most robust science, eroding regulatory confidence and stalling a program. Guidance on drug master files underscores the need for clear and complete documentation, as this information is used by regulatory agencies to assess the manufacturing process (11).

Example 1: one new drug application was delayed when reviewers found inconsistencies between batch records and process descriptions. In this case, impurity limits were not adequately justified, and the history of excipient sourcing was ambiguous.

Example 2: the ability to trace every component of a drug to its source is non-negotiable for patient safety. Yet, one biologics license application was refused at filing due to incomplete traceability of raw materials used in pivotal clinical batches.

Solution: master the regulatory narrative

Engaging with regulators throughout the process can help sponsors prioritize documentation from the start, ensuring that every detail tells a coherent story that builds regulatory confidence. A meticulously maintained paper trail is as important as the quality of the product itself; without it, the regulatory review process can be brought to a halt. FDA guidance on CMC information for biotech products outlines the specific types of data needed to ensure a smooth review (11).

Moving past rare successes to treating rare diseases

The successful approval of an orphan drug is a milestone worth celebrating, but it is too often treated as a rare event. The industry’s true goal is to move beyond individual successes and establish a reliable, repeatable process for delivering therapies to rare disease patients. The common CMC problems outlined in this article are not just technical issues; they are obstacles that steal momentum and create costly detours. By addressing them proactively, sponsors can transform the development process, and strategic collaboration with partners experienced in end-to-end orphan drug development can be a key part of that. Ultimately a focus on operational excellence is what ensures that a groundbreaking therapy is not lost to a preventable mistake, joining the dots between processes and patients who have already had to be patient for far too long.

References

1. The Lancet Global Health. The Landscape for Rare Disease in 2024. 2024 12 (3). https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(24)00056-1/fulltext
2. FDA. 21 CFR Part 316. https://www.govinfo.gov/content/pkg/FR-2013-06-12/pdf/2013-13930.pdf
3. ICH. Q8(R2) Pharmaceutical Development (ICH, 2009).
4. ICH. Q9 Quality Risk Management (ICH, 2005).
5. ICH. Q11 Development and Manufacture of Drug Substances (ICH, 2012).
6. FDA. CMC Information for Human Gene Therapy INDs, Guidance for Industry (FDA, 2020).
7. Kumar M.; et al. CMC Challenges in Gene and Cell Therapy. Mol Ther Methods Clin Dev. 2020 17:523–530.
8. EMA. Quality Documentation for Biological IMPs (EMA, 2022).
9. PDA. Technical Report 60-2: Process Validation Lifecycle (PDA, 2021).
10. EMA. Process Validation for Finished Products (EMA, 2016).
11. FDA. CMC Information and Establishment Description for Biotech Products. (FDA, 2023).

About the author

Hibreniguss Terefe, is director, Product Development Somerset at Ardena.

Komunikasi antara pabrik manufaktur dan toko ritel. | Kredit Gambar: © Cagkan – © Cagkan – stock.adobe.com

ICE Pharma, produsen API, eksipien, dan bentuk sediaan jadi yang berasal dari asam empedu, mengumumkan pada 15 Oktober 2025 bahwa mereka akan memamerkan inovasi dan strategi keberlanjutannya di Booth 9.1 A94 di CPHI Frankfurt 2025, yang diadakan pada 28-30 Oktober. Sorotan meliputi produksi asam ursodeoksikolat (UDCA) dan turunan asam empedu (1).

Produk ICE membantu aplikasi terapeutik untuk penyakit hati, metabolisme, dan saraf dan dikembangkan di lima pusat penelitian dan pengembangan perusahaan. Perusahaan juga memiliki kerangka kualitas untuk memastikan ketertelusuran, inaktivasi virus, sistem manufaktur tertutup, dan kepatuhan terhadap peraturan.

Bagaimana ICE Pharma memenuhi tujuan keberlanjutan?

ICE Pharma akan memaparkan empat pilar strategi keberlanjutannya: Memerangi Penyakit melalui Inovasi Produk, Peduli terhadap Manusia, Mempercepat Operasi Berkelanjutan, dan Membangun Hubungan yang Kuat. Perusahaan menggunakan strategi ini untuk mengambil keputusan terkait pengelolaan sumber daya, pengurangan limbah, sumber energi, dan keterlibatan pemangku kepentingan. Mengikuti filosofi pengurangan, penggunaan kembali, daur ulang, ICE akan menghadirkan stan berdesain ramah lingkungan di CPHI Frankfurt yang dibangun dari bahan-bahan yang dapat didaur ulang dari acara-acara sebelumnya, sehingga meminimalkan dampak lingkungan.

“Di ICE Pharma, tanggung jawab kualitas dan lingkungan tidak dapat dipisahkan,” kata Agostino Barazza, Chief Executive Officer. “Dengan menguasai asam empedu melalui kontrol yang ketat dan desain yang berkelanjutan, kami menghadirkan obat-obatan yang berdampak dan berintegritas.”

“Peta jalan keberlanjutan kami memperkuat operasi dan menginspirasi kepercayaan di seluruh rantai pasokan kami, memberdayakan mitra untuk memberikan terapi yang memanfaatkan ilmu asam empedu,” tambah Roger Viney, Chief Commercial Officer.

Apa lagi yang ditampilkan ICE Pharma di acara tersebut?

ICE akan merayakan ulang tahun keseratus ABC Farmaceutici di CPHI Frankfurt, yang didirikan pada tahun 1925 di Turin dan diakuisisi oleh ICE pada tahun 2021 (2). ABC Farmaceutici akan menyoroti pencapaian dan konsentrasi penelitiannya pada acara tersebut. Logo khusus “100 Tahun” juga akan diluncurkan pada konferensi tersebut.

“Mencapai usia 100 tahun bukan hanya sekedar perayaan masa lalu kita, tapi juga janji masa depan,” kata Severino Previtali, direktur Unit Bisnis ABC Farmaceutici, dalam siaran persnya (3). “Pencapaian ini mengingatkan kita pada generasi-generasi yang telah berkontribusi terhadap kesuksesan kita, dan menginspirasi kita untuk terus mendorong inovasi, membangun kolaborasi yang kuat, dan memberikan dampak yang berarti terhadap kesehatan global.”

Apa pendekatan ICE Pharma terhadap kualitas?

Sebagai bagian dari cakupan DCAT, Teknologi Farmasi berbicara dengan Roger Viney, chief komersial officer ICE Pharma, tentang masalah kualitas dan kepatuhan seputar penggunaan bahan-bahan yang berasal dari hewan dalam industri bio/farmasi (4). Dalam wawancara tersebut, Viney berbicara tentang pentingnya harmonisasi peraturan dan meningkatkan keamanan rantai pasokan. Beliau juga menyampaikan tentang pentingnya ketertelusuran dan mengetahui asal usul bahan yang berasal dari hewan. Wawancaranya bisa dilihat di sini.

Referensi

1. Farmasi ES. ICE Pharma Menyoroti Keberlanjutan dan Keahlian Asam Empedu di CPhI Worldwide 2025. Siaran Pers. 15 Oktober 2025.
2. Lavery, P. ABC Farmaceutici Akan Menandai Hari Jadi ke-100 dengan CPHI Frankfurt Display. FarmasiTech.com. 18 September 2025. https://www.pharmtech.com/view/abc-farmaceutici-mark-100th-anniversary-cphi-frankfurt-display
3. Farmasi ES. ABC Farmaceutici Merayakan 100 Tahun Keunggulan dan Inovasi Farmasi. Siaran Pers. 17 September 2025.
4. Thomas, F. DCAT Week 2025: Kualitas dan Kepatuhan untuk Produk Berasal dari Hewan. FarmasiTech.com. 18 Maret 2025.

Industri alat penghirup dosis terukur bertekanan (pMDI) sedang mengalami salah satu transformasi paling signifikan dalam beberapa dekade dengan peralihan ke propelan generasi berikutnya (NGP). Bergabunglah dengan Kindeva untuk mengeksplorasi bagaimana fasilitas luar biasa, keahlian pMDI selama puluhan tahun, dan panduan strategis dapat membantu para inovator menavigasi perubahan ini dengan percaya diri.

Daftar Gratis: https://www.pharmtech.com/pt_w/propellants

Ikhtisar Acara:

Pergerakan global menuju propelan generasi berikutnya (NGPs) mewakili momen penting bagi pengembang obat paru, dimana tekanan peraturan dan komitmen keberlanjutan mendorong perubahan yang cepat. Dalam webinar ini, para ahli Kindeva akan menguraikan bagaimana warisan mendalam perusahaan dalam pemberian obat inhalasi dan investasinya pada fasilitas canggih secara unik memposisikannya untuk mendukung pelanggan melalui transisi ini. Peserta akan mendapatkan wawasan tentang tantangan dan peluang dalam mengadopsi NGP, serta panduan praktis tentang cara memanfaatkan kemampuan Kindeva, mulai dari formulasi dan pengembangan perangkat hingga pasokan klinis dan manufaktur skala komersial. Dengan menyoroti fasilitas dan kemampuan baru Kindeva, sesi ini akan menunjukkan bagaimana perusahaan bermitra dengan pelanggan untuk memastikan terapi paru yang siap di masa depan, patuh, dan berpusat pada pasien.

Tujuan Pembelajaran Utama:

• Pahami faktor-faktor yang mendorong transisi industri ke NGP, termasuk peraturan dan lanskap sosial yang menyebabkan peralihan tersebut.
• Pelajari bagaimana kemampuan CDMO desain Kindeva yang luar biasa dan manufaktur NGP skala klinis ke skala komersial dapat memungkinkan transisi yang mulus dan dipercepat.
• Jelajahi kantor pusat pMDI Kindeva yang baru dan temukan bagaimana teknologi mutakhir dan solusi CDMO komprehensif kami menyediakan pengembangan dan manufaktur produk pMDI yang skalabel dan berkelanjutan kepada pelanggan.

Siapa yang Harus Hadir:

• Direktur penjaminan mutu/mutu
• Kepala kontrol kualitas
• Wakil presiden kualitas
• Wakil presiden senior bidang penelitian, peneliti utama, kepala penelitian, wakil presiden penelitian, direktur penelitian senior
• Direktur/kepala manufaktur, kepala operasi, presiden, CEO, direktur pelaksana
• Wakil presiden sumber global, kepala pejabat pengadaan, direktur pengadaan
• Direktur pengembangan bisnis, wakil presiden penjualan komersial, wakil presiden penjualan regional
• Kepala laboratorium, insinyur biomedis, ahli biokimia, kepala petugas ilmiah, kepala petugas teknologi

Pembicara:

Craig Sommerville
Wakil Presiden Senior, MDI
Kindeva

Craig Sommervillewakil presiden senior unit bisnis metered-dose inhaler (MDI) Kindeva, bertanggung jawab untuk membentuk dan melaksanakan strategi global platform MDI, dengan fokus memimpin industrialisasi transisi propelan ramah lingkungan. Dengan pengalaman lebih dari 25 tahun dalam berbagai peran senior di bidang kepemimpinan lokasi, strategi rantai pasokan, operasi, logistik, pengadaan, dan fungsi teknis, Sommerville memiliki rekam jejak yang terbukti dalam mengubah tantangan menjadi peluang.

Daftar Gratis: https://www.pharmtech.com/pt_w/propellants

Bidikan Sudut Tinggi Meja Kerja Orang Sukses di Kantor dengan Pemandangan Jendela Pemandangan Kota. | Kredit gambar: © Gorodenkoff – stock.adobe.com

Industri farmasi berada dalam periode transformasi yang cepat, didorong oleh inovasi ilmiah, ekspektasi peraturan, dan meningkatnya kompleksitas terapi. Masalah ini menyoroti tren paling mendesak yang membentuk sektor ini dan strategi yang diterapkan organisasi agar tetap kompetitif.

Dalam cerita sampul kami, Susan Haigney mengeksplorasi pendekatan inovatif terhadap bioanalisis, di mana otomatisasi dan metodologi baru memperluas kemampuan untuk mendapatkan hasil yang lebih cepat dan andal. Ketika kompleksitas modalitas obat meningkat, inovasi bioanalitis tidak lagi menjadi pilihan; hal ini penting untuk memastikan keamanan produk, kepatuhan terhadap peraturan, dan kecepatan pengembangan.

Yang juga penting adalah pengembangan formulasi. Cynthia Challener meneliti bagaimana kecerdasan buatan (AI) dan pembelajaran mesin diterapkan pada pemodelan prediktif untuk molekul kecil, di mana kandidat obat menghadirkan tantangan berat dalam kompleksitas dan penyampaian molekul.

Kemajuan dalam digitalisasi dan otomatisasi pemrosesan aseptik membantu organisasi mengatasi semakin beragamnya produk obat suntik. Pendekatan yang disederhanakan dan didukung teknologi mengurangi intervensi manusia, meningkatkan jaminan sterilitas, dan meningkatkan skalabilitas.

Edisi ini juga menyelidiki pemodelan mekanistik pembersihan ginjal, dengan Akanksha Prasad memberikan wawasan tentang optimalisasi strategi pemberian dosis untuk pasien lanjut usia. Seiring bertambahnya usia populasi pasien, jenis penelitian ini sangat penting untuk menyeimbangkan kemanjuran dan keamanan dalam perawatan klinis.

Integrasi data dan transformasi digital tetap menjadi hal penting bagi kemajuan industri ini. Jennifer Markarian menyoroti bagaimana penggunaan data proses yang lebih baik, yang ditingkatkan oleh AI dan analitik tingkat lanjut, memungkinkan kontrol proses yang lebih cerdas dan sistem manufaktur yang lebih terhubung.

Patrick Lavery meneliti dorongan FDA untuk meningkatkan kualitas, integritas, dan keseragaman, khususnya dalam konteks manufaktur maju dan pengendalian batch. Bagian Tanya Pakar kami membahas pentingnya bukti nyata yang digunakan dalam farmakovigilans.

Seperti yang ditunjukkan oleh artikel-artikel ini, masa depan farmasi terletak pada keseimbangan yang cermat: mengadopsi teknologi mutakhir sambil menjunjung standar kualitas dan keamanan yang ketat. Organisasi yang sukses adalah organisasi yang merangkul inovasi dan menjadikan pasien sebagai pusat dalam setiap pengambilan keputusan.

Tentang penulis

Mike Hennessy Jr adalah Ketua dan CEO MJH Life Sciences®.

Detail artikel

Teknologi Farmasi®
Jil. 49, No.8
Oktober 2025
Halaman: 8

Kutipan

Saat merujuk pada artikel ini, mohon kutip sebagai Hennessy, M. Dari Penemuan hingga Pengiriman: Praktik yang Berkembang di Farmasi. Teknologi Farmasi 2025 49 (8).

Gedung Putih – Washington DC Amerika Serikat | Kredit Gambar: © Orhan Çam – stock.adobe.com

AstraZeneca telah setuju untuk menawarkan obat-obatan dengan harga yang lebih rendah, “negara yang paling disukai” (MFN) kepada pasien di Amerika Serikat melalui platform TrumpRx.gov milik pemerintah federal yang belum beroperasi, kata seorang pejabat Gedung Putih kepada MSNBC pada hari Jumat, 10 Oktober 2025 (1). Laporan MSNBC menyebutkan bahwa kantor pers Gedung Putih menolak memberikan komentar resmi.

Situs web RollCall.com menerbitkan jadwal publik Presiden AS Donald Trump pada 10 Oktober, yang mengindikasikan bahwa presiden akan membuat pengumuman di Ruang Oval pada pukul 5 sore ET (2). MSNBC melaporkan bahwa sumbernya di Gedung Putih mengatakan CEO AstraZeneca Pascal Soriot akan bertemu dengan Trump pada sore hari tanggal 10 Oktober, dan hadir untuk pengumuman Gedung Putih (1).

Detail apa saja yang dilaporkan mengenai perjanjian AstraZeneca?

Kesepakatan AstraZeneca yang dilaporkan untuk menurunkan harga obat di AS bertujuan untuk membuat resep lebih terjangkau bagi pasien dengan pendapatan rendah, termasuk mereka yang menggunakan Medicaid, menurut laporan MSNBC (1). Platform TrumpRx akan memungkinkan perusahaan mana pun yang mencapai kesepakatan MFN dengan Gedung Putih untuk menjual obat-obatan mereka langsung ke konsumen dengan diskon besar, menurut pejabat pemerintah lain yang dihubungi oleh MSNBC, tetapi situs web tersebut diperkirakan baru akan tersedia pada tahun 2026.

Pfizer adalah perusahaan farmasi pertama yang mengumumkan perjanjian MFN dengan Gedung Putih, yang diungkapkan kedua belah pihak pada 30 September 2025 (3). Hal ini terjadi satu hari setelah berakhirnya jangka waktu 60 hari yang ditetapkan Trump bagi perusahaan-perusahaan untuk mematuhi proses langkah demi langkah, yang disediakan oleh pemerintahannya, untuk menurunkan harga obat resep di AS ke harga terendah yang ditawarkan di antara negara-negara maju lainnya, atau pemerintah federal akan “menerapkan setiap alat yang ada di gudang senjata kami untuk melindungi keluarga Amerika dari praktik penetapan harga obat yang sewenang-wenang” (4).

Selain AstraZeneca dan Pfizer, 15 perusahaan lain yang menerima surat yang menguraikan rencana tersebut adalah AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, EMD Serono, Genentech, Gilead Sciences, GSK, Johnson & Johnson, Merck & Co., Novartis, Novo Nordisk, Regeneron, dan Sanofi (4).

Komitmen apa lagi yang dimiliki AstraZeneca di AS?

Kesepakatan yang akan segera terjadi dengan Gedung Putih adalah berita besar kedua yang melibatkan AstraZeneca dalam beberapa hari ini. Pada tanggal 9 Oktober 2025, perusahaan tersebut mengatakan akan menginvestasikan total $4,5 miliar di fasilitas manufaktur baru di AS, dekat Charlottesville, Virginia, dengan jumlah uang tersebut mewakili usulan peningkatan sebesar $500 juta yang akan didedikasikan untuk meningkatkan kemampuan manufaktur yang mendukung lebih banyak obat-obatan, termasuk pengobatan kanker (5). Investasi tersebut hanyalah sebagian dari keseluruhan komitmen AstraZeneca sebesar $50 miliar terhadap manufaktur dan penelitian dan pengembangan AS yang pertama kali diumumkan pada Juli 2025, sebagai bagian dari peninjauan ulang operasi manufaktur secara luas di industri akibat perubahan kebijakan tarif pemerintahan Trump.

Cerita ini akan diperbarui.

Referensi

1. Traylor, J. Trump Membuat Kesepakatan Harga Obat dengan Raksasa Farmasi AstraZeneca. MSNBC.com10 Oktober 2025.
2. Roll Call Fakta.se. Jadwal Publik Donald J. Trump. RollCall.comdiperbarui 10 Oktober 2025.
3. Lavery, P. Pfizer Mencapai Kesepakatan Pertama dengan Gedung Putih mengenai Penetapan Harga MFN; Siapa yang Akan Menjadi Selanjutnya? FarmasiTech.com30 September 2025.
4. Lavery, P. Trump Mengirim Surat ke 17 Perusahaan Farmasi Terkemuka yang Menjelaskan Protokol Penetapan Harga Obat Paling Disukai Bangsa. FarmasiTech.com1 Agustus 2025.
5. Lavery, P. Ekspansi AstraZeneca di AS Menyoroti AI, Otomatisasi, dan Tekanan Kebijakan dalam Manufaktur Farmasi. FarmasiTech.com10 Oktober 2025.

Many multi-colored pills in a Senior’s hands. Painful old age. Caring for the health of the elderly | Image Credit: ©perfectlab – stock.adobe.com

Abstract

The kidneys serve as the primary excretory organs responsible for eliminating endogenous waste products and xenobiotics, including pharmaceutical agents and their metabolites, through urine formation. Understanding the mechanistic basis of renal drug excretion is crucial for optimizing therapeutic efficacy and minimizing toxicity. This paper provides an in-depth overview of the anatomical structure and functional dynamics of renal filtration, secretion, and reabsorption processes that govern drug clearance. Blood is delivered to the kidneys via the renal artery, and filtration begins at the glomerulus where small molecules pass into the nephron while larger components remain in circulation. The filtrate undergoes further refinement through selective tubular reabsorption and active secretion, culminating in urine formation. The role of the nephron in modulating drug excretion is modeled mathematically using key pharmacokinetic parameters, including the glomerular filtration rate, free drug fraction, intrinsic tubular clearance, and the area under the plasma drug concentration-time curve. This work also presents fundamental equations describing renal clearance pathways and explores factors influencing drug reabsorption and secretion. Together, these insights offer a quantitative framework for predicting renal drug clearance and guiding rational drug design and dosage regimen development.

Peer-Reviewed

Submitted: June 29, 2025

Accepted: August 13, 2025

Blood is composed of plasma, red blood cells, white blood cells, and platelets. The normal 70-kg adult has 5 L of blood (0.07 L/kg), roughly 55% of which is a liquid called plasma, and 45% is cells and platelets. The kidney is the primary organ of discharge of the body’s byproducts, and of medications and medication metabolites. Urine is the main liquid for the discharge of waste materials (coming out from different cell processes), as well as medications and metabolites, from the body.

The kidney is the primary organ for excretion of the body’s byproducts, medications, and medication metabolites (see Figure 1). Urine serves as the final pathway for eliminating metabolic byproducts, drugs, and their metabolites from the body.

Figure 1: Mechanistic model of renal clearance processes for daptomycin. Figures created with AI and courtesy of the author

Blood flows into the kidney through the renal artery. This large blood vessel branches into smaller vessels until the blood reaches the nephrons. In the nephron, blood is filtered by the tiny vessels of the glomeruli and then flows out of the kidney through the renal vein. In a single day, the kidneys filter about 140 L of blood. Most of the water and other substances that filter through the glomeruli are returned to the blood by the tubules. Only 1–2 L become urine (1).

Each nephron is divided into two sections: the renal corpuscle and renal tubule. As blood flows into each nephron, it enters a cluster of tiny blood vessels—the glomerulus. The thin walls of the glomerulus allow smaller molecules, wastes, and fluid—mostly water—to pass into the tubule. Larger molecules, such as proteins and blood cells, stay in the blood vessel.

Reabsorption and secretion adjust the composition and volume of glomerular filtrate as it travels down the nephron to the collecting tubule. When these processes are completed, the concentrated filtrate, now called urine, is moved to the bladder for storage until it is eliminated from the body.

As the global population ages, integrating physiological modeling into early stage drug development and dose planning has become essential for tailoring therapies to vulnerable subpopulations.

Methods

Model framework. Renal clearance (2) was modeled as the sum of three components as shown in Equation 1.

(Eq. 1)

Where:

CLfiltration = clearance via glomerular filtration

CLsecretion = clearance via tubular secretion

CLreabsorption = reabsorption (negative contribution to clearance).

A schematic representation of method for glomerular filtration, tubular secretion, and reabsorption is shown in Figure 2.

Figure 2: Schematic representation of renal clearance model. Figures created with AI and courtesy of the author

Equations. Equation 1 expresses total renal clearance as the net result of filtration, active secretion, and reabsorption. Mechanistic renal clearance is shown in Equation 2.

(Eq. 2)

Where:

CLR = renal clearance

Fu = fraction unbound

Q = renal blood flow

CLi = intrinsic renal clearance

Fr = fraction of compound reabsorbed from tubule.

Free fraction (fu). Equation 3 defines the fraction of unbound (free) drug in plasma. Only unbound drug is pharmacologically active and subject to filtration, secretion, or metabolism.

(Eq. 3)

Glomerular filtration clearance (CL_GF). Equation 4 shows that the clearance due to glomerular filtration is directly proportional to the free fraction and the glomerular filtration rate.

(Eq. 4)

Tubular secretion clearance (CL_TS). Equation 5 models active secretion into the renal tubule, where QR′ is renal plasma flow, CLu_int is intrinsic unbound renal clearance, and C is the drug’s plasma concentration.

(Eq. 5)

Tubular reabsorption (passive). Equation 6 shows the influence of urinary pH and drug pKa on passive reabsorption. Non-ionized (lipophilic) species are more readily reabsorbed.

(Eq. 6)

Overall renal clearance (CLr). Equation 7 allows the calculation of the net renal clearance based on the excretion rate or total excreted amount (Ae) relative to plasma exposure (AUC), with the method shown in Figure 2.

(Eq. 7)

Drug parameters: daptomycin. Daptomycin is a cyclic lipopeptide antibiotic indicated for the treatment of complicated skin and skin-structure infections, Staphylococcus aureus (S. aureus) bacteremia, and right-sided infective endocarditis caused by susceptible Gram-positive organisms, including methicillin-resistant S. aureus (MRSA) (3). It is administered intravenously and is particularly valuable for patients who cannot tolerate or have failed other antibiotic therapies.

However, the following physicochemical properties (4) limit daptomycin’s oral absorption and influence its pharmacokinetics:

• high polarity
• low lipid solubility
• high molecular weight
• high protein binding (low fu)
• primary elimination via renal excretion.

Model calibration and validation. Model parameters, including volume of distribution (Vd), glomerular filtration rate (GFR), and tubular secretion capacity, were obtained from published pharmacokinetic studies on daptomycin (5). These values were iteratively adjusted within physiological bounds to achieve close agreement with observed plasma concentration-time profiles.

Simulations were conducted for two populations:

• young adults (18–30 years): assumed normal GFR (~125 mL/min/1.73 m²) and intact tubular function
• geriatric adults (>70 years): modeled with a 30% decline in GFR and reduced tubular secretion, reflecting known physiological changes with aging.
• The model outputs, including renal clearance (CLr) and plasma concentration profiles, were compared against reported clinical pharmacokinetic data to validate predictive accuracy.

Clearance was calculated for two populations:

• young adults (18–30 years): normal GFR and secretion
• geriatrics (>70 years): 30% reduction in tubular secretion, age-related decline in GFR.

Volume of distribution (Vd) and other parameters were taken from literature values and adjusted to fit experimental data.

The modeled clearance for young adults was CLr = 16.2 mL/min/kg. Predicted clearance aligned well with reported pharmacokinetic data for daptomycin in healthy adult volunteers.

Results

Young adults. In this analysis, the young adult group refers to individuals aged 18–30 years. Using the slope of the plasma concentration–time curve together with the estimated volume of distribution (Vd​), the renal clearance (CLr​) was calculated according to Equation 1. This calculation resulted in a CLr​ value of 16.2 mL/min/kg for the young adult population.

Figures 3 and 4 depict the mean plasma concentration–time profiles of Daptomycin in young and elderly adults, respectively, modeled using the renal clearance equation (Eq. 1). In this analysis, the geriatric group refers to individuals over 70 years of age. Using the same calculation method described in Equation 1, the CLr for this group was determined to be 9.2 mL/min/kg as shown in Tables I and II.

Figure 3: Daptomycin plasma concentration in young adults (mean profile). Figures created with AI and courtesy of the author

Table I. Modeled and documented renal clearance (CLr ) and percent error for young and elderly populations.

Geriatric population. Initial model over-predicted clearance: CLr = 12.8 mL/min/kg (calculated using Equation 1). After incorporating a 30% reduction in tubular secretion, CLr = 9.2 mL/min/kg. This adjustment brought the model into closer agreement with known clearance values for elderly patients.

Figure 4: Daptomycin plasma concentration in geriatric adults (mean profile). Figures created with AI and courtesy of the author

Table II. Why the Error? (As per Figures 3 and 4). Summary of model error sources for young and elderly populations.

Model performance and clinical implications. The model effectively reproduced published plasma concentration–time data for both young and elderly populations, with a percent error (6) of

These findings underscore the importance of modeling tubular secretion decline in elderly patients, which is often overlooked in simpler renal clearance models.

Clinical implication. For drugs such as daptomycin that are primarily eliminated renally, failure to adjust dosing in geriatric populations may lead to drug accumulation, prolonged exposure, and increased toxicity risk. Model-guided predictions can aid in personalized dosing and safer therapeutic outcomes in age-diverse patient populations.

The model successfully captured the qualitative and quantitative effects of aging on daptomycin clearance. Errors in prediction primarily arose from uncertainties in the estimation of fu, tubular secretion rates, and reabsorption dynamics.

Failure to adjust dosing in renally impaired geriatric patients can result not only in elevated plasma concentrations and toxicity, but also in subtherapeutic exposure if assumptions about drug half-life are inaccurate. For antibiotics such as daptomycin, improper dosing can increase the risk of treatment failure, resistance development, and adverse effects such as nephrotoxicity and rhabdomyolysis.

Discussion

This study demonstrates that incorporating detailed renal physiology into pharmacokinetic models can accurately predict clearance variability across age groups. The results underscore the importance of tubular secretion and its decline with aging—a factor sometimes overlooked in simpler models.

Clinical implications include the need for dose adjustments in elderly patients to prevent accumulation and toxicity, particularly for drugs such as daptomycin that rely heavily on renal excretion.

Limitations of the model include simplifications of nonlinear reabsorption and potential age-related changes in plasma protein binding. Future work will extend the model to account for these factors and validate predictions against clinical data.

The close agreement between predicted and literature-reported (5) Cmax and AUC (Figures 5 and 6) provides confidence in the model’s applicability for dose adjustment in elderly populations.

Figure 5: Comparison of predicted vs. literature-reported maximum plasma concentrations (C_max) for daptomycin in young adults and elderly subjects. Predicted values are based on renal clearance modeling integrating age-related glomerular filtration rate decline. Figures created with AI and courtesy of the author

Limitations of the model include simplifications of nonlinear reabsorption and potential age-related changes in plasma protein binding. Validation against clinical data will be essential to strengthen the model’s applicability. While the model accurately captures average trends in renal clearance, it assumes linear pharmacokinetics and constant plasma protein binding, which may not reflect pathophysiological changes in elderly patients with comorbidities. Future extensions could incorporate nonlinear reabsorption, saturable transport kinetics, and patient-specific variables.

Figure 6: Comparison of predicted vs. literature-reported area under the plasma concentration–time curve (AUC) for daptomycin. The increased AUC in elderly patients reflects reduced renal clearance and longer systemic exposure. Figures created with AI and courtesy of the author

Conclusion

Mechanistic modeling of renal clearance provides a powerful tool for understanding and predicting pharmacokinetic variability. The approach presented here accurately captured age-related declines in daptomycin clearance and can be generalized to other renally cleared drugs. This work supports the broader goal of individualized dosing and precision pharmacotherapy:

• Accurate quantification of tubular secretion and reabsorption remains challenging due to limited clinical data.
• Properties such as lipophilicity, polarity, plasma binding, and molecular size play a big role in how easily a drug is excreted renally.
• Reduction in kidney function, whether from disease, age, or another factor, can lead to build up of drug, which means it takes a longer time for it to be eliminated.
• Polarity as well as fu can help predict total clearance, as in, a drug that is highly plasma bound will likely need to be metabolized, and a polar molecule is more readily secreted.

This model offers a predictive tool for quantifying age-related variability in renal drug clearance, with potential clinical applications in guiding dose adjustment for elderly patients receiving renally excreted therapies such as daptomycin. By integrating physiological parameters and real-world pharmacokinetic data, this approach supports the broader goal of individualized dosing and improved therapeutic outcomes.

Availability of data and materials

This manuscript does not report new datasets. All data used in the modeling and simulations were obtained from published sources as referenced in the manuscript. No additional data are available.

References

1. Tucker, G. Measurement of the Renal Clearance of Drugs. Br J Clin Pharmacol. 1981 12:761–770.
2. Dvorchik, B.H.; Brazier, D.; DeBruin, M.F.; et al. The Pharmacokinetics of Daptomycin in Young and Elderly Adults. Clin Pharmacokinet. 2003 42(6):673–684. DOI:10.2165/00003088-200342060-00006
3. National Kidney Foundation. Estimated Glomerular Filtration Rate (eGFR). 2015. kidney.org/atoz/content/gfr. (accessed Aug 14, 2025).
4. Ye, M.; Nagar, S.; Korzekwa, K. A Physiologically Based Pharmacokinetic Model to Predict the Pharmacokinetics of Highly Protein-Bound Drugs and the Impact of Errors in Plasma Protein Binding. Biopharm Drug Dispos. 2016 37:123–141.
5. Levison, M.E.; Levison, J.H. Pharmacokinetics and Pharmacodynamics of Antibacterial agents. Infect Dis Clin North Am. 2009 23:791–vii.
6. FDA. Cubicin (Daptomycin) (Prescribing Information). Silver Spring, MD: FDA. www.accessdata.fda.gov (accessed Aug 14, 2025).

About the author

Akanksha Prasad, MS, is a chemical and bioprocess engineer with over nine years of experience in chemical, biologics, and pharmaceutical process development. Her expertise spans mRNA, vaccines, and biologics, with a focus on technology transfer, PAT, scale-up, purification, and regulatory compliance. She holds a Master’s in Chemical Engineering with a biopharma specialization from the Illinois Institute of Technology, Chicago, and a Bachelor’s in Chemical Engineering from India.

Article details

Pharmaceutical Technology®
Vol. 49, No. 8
October 2025
Pages: 21–27

Citation

Prasad, A. Mechanistic Modeling of Renal Clearance: Optimizing Dosing Strategies for Elderly Patients. Pharmaceutical Technology 2025 49 (8).

A scientist in sterile coverall gown using a daily checklist check the cleanroom condition status in laboratory. Cleanroom facility. | Image Credit: ©warut – Stock.Adobe.com

As the number of biologic drugs has grown in the pharmaceutical pipeline and market, aseptic manufacturing capabilities have steadily grown in importance. Assuring sterility across many different modalities and product formats/sizes/volumes (e.g., vials, cassettes, prefilled syringes/pens, microdosing systems, intranasal delivery systems, on-body devices, bags, etc.), many of which are increasingly potent, has also become more challenging. Innovation in processing technologies has been essential to address the evolving needs of manufacturers. Key areas of development have included digitalization and automation solutions.

Repeatability and speed with improved quality and yield

Digitalization and automation provide numerous benefits to aseptic processing operations. Two of the most important, according to Alex Strauss, senior principal process equipment engineer with Curia, are greater speed combined with improved repeatability. “The key to automation is having a recipe-driven approach that is qualified. When the operator selects the recipe, the process is then repeatable. In addition, processes such as visual inspection can be completed much more rapidly than is possible by human operators and with incredible accuracy,” he explains.

New filling systems, adds Tom Clemens, senior director of engineering and facilities at Lifecore Biomedical, perform non-destructive weight checks of individual products immediately after filling, improving quality and increasing batch yields. Many also include automated camera verification systems to check vial crimping and stopper placement. “When an issue is detected, the system can automatically stop the line so the problem can be investigated immediately, avoiding costly material losses and potentially much longer production delays,” he says.

Impact of growing isolator adoption

Many newer biologic products, including antibody-drug conjugates, radio-immunoconjugates, and cell and gene therapies, require high containment solutions to ensure operator safety. The diversity of products with high activity produced in multiproduct facilities has also created the need for effective solutions that reduce cross-contamination risks.

Regulations such as Annex 1 requirements in the European Union (1) have also been an important driver toward greater adoption of isolator technology to increase product safety by minimizing potential human impacts on sterile drug products, according to Clemens. Many manufacturers have therefore been shifting to the use of isolators for aseptic processing.

“Due to the nature of these closed, isolator-based filling systems, automation and robotics have been incorporated to perform necessary processing steps within the sterile environment,” Clemens observes. For instance, he notes that while older systems may have required an operator to remove a lid from a ready-to-use (RTU) tub of vials or syringes, many new isolator fillers use automated systems that heat the lid adhesive and then remove the lid from the tub with a variety of rollers. “This approach,” Clemens states, “reduces human contact and potential particle generation.”

Automated visual inspection

Visual inspection operations are another area that has benefited significantly from advances in automation and digitalization technologies. These automated visual inspection systems use high-speed cameras and advanced software to automatically check for particulates and defects and can operate at fairly high speeds, according to Strauss. The Syntegon system deployed at Curia’s Albuquerque, NM facility, for instance, can inspect 400 vials per minute, matching the filling system’s filling speed.

As importantly, newer automated visual inspection systems are now available that can reliably evaluate highly viscous formulations (in excess of 100,000 centipoise) in vials and syringes, which they were previously not able to do. “Traditional automated visual inspection systems spin a vial/syringe and rely upon a camera to enable evaluation of the internal movement of the product to identify contaminants, which is not a suitable approach for viscous formulations because they do not flow in the same manner as lower viscosity solutions,” Clemens explains. Newer systems, he comments, incorporate additional cameras and advanced virtual image processing to identify particulates and defects and can even improve performance over time by incorporating machine learning algorithms.

Robotics simplify operations

Robotic systems do not just support the incorporation of aseptic filling processes within isolators and visual inspection activities. They have been widely implemented in sterile drug manufacturing processes to automate many different repetitive tasks, including vial filling, sealing, and labeling. By automating these activities, human interaction with sterile drug products is minimized, reducing contamination risks. Furthermore, robotic systems minimize product losses and enable the accurate filling of products that require only very small volumes.

Robotic systems can also eliminate some of the steps required when human operators are more involved in the aseptic filling process. For instance, the VarioSys Flex Line system at its Albuquerque, NM facility uses robotics to remove vials from a pre-sterilized tub, eliminating the need for a vial washer and sterilizing tunnel, according to Eric Schneider, director of global equipment engineering at Curia.

“In manually operated systems, it is not possible to aseptically remove primary containers without obstructing the first air (uninterrupted unidirectional filtered airflow used to provide a sterile environment) and/or subjecting the vials to scratches, etc., thus creating the need for additional steps,” Schneider says. With the VarioSys Flex Line, operator interventions are minimized, simplifying the process while also affording improved quality and safety outcomes.

Schneider does caution, however, that even the best robotics and automation systems still rely on human operators. “Training programs for operators are essential,” he emphasizes. To address this need, Curia operates Sterile University, a program designed to provide both training for new employees and continuing education for all manufacturing and quality staff through a simulated manufacturing environment that replicates the facilities, equipment, operations, and protocols found at the company.

Improvements in automated and digitized analytics

Automation and digitalization of analytics that support aseptic processing has several benefits as well. One of them, according to Jon Kallay, senior scientific portfolio specialist for microbial solutions with Charles River Laboratories, has been the facilitation of the adoption of rapid testing techniques that enable faster product release while still ensuring product quality.

One challenge with complex biologics highlighted by Kallay is the tendency for these products to appear turbid during routine sterility testing due to their physicochemical properties. Identification of such turbidity during manual visual inspection operations typically prompts a lengthy evaluation process to confirm the turbidity is not due to contamination.

Rapid test methods that evaluate multiple attributes, such as detection of adenosine triphosphate, respiration, and other microbial indicators, when combined with automated analysis of test results, provide accurate indicators and eliminate the subjective aspect of test results, Kallay contends. “Analysts no longer need to shake a bottle and determine if it fits their understanding of ‘turbid.’ Results are automatically analyzed and determined to be positive or negative based on the standards established during the validation of the technology,” he says. “Objective results eliminate unnecessary procedures while allowing quick release of product to patients,” Kallay concludes. In addition, more rapid access to test results allows users to respond quickly to any contamination events that could impact the facility and other product lots.

Digitizing the test process also improves data integrity. Documentation errors are not uncommon when test results are managed manually, according to Kallay. With digital test technologies, however, test materials and results are immediately documented and automatically transcribed to the laboratory information management system (LIMS) data storage system, avoiding opportunities for operator error.

Real-time monitoring is a game-changer

The ability to collect real-time manufacturing data during aseptic processing has been, according to Clemens, a real game-changer, as it has made it possible to monitor quality in a proactive rather than a reactive manner. Lifecore Biomedical, for instance, uses a dashboard approach displayed on monitors throughout the facility to keep a watchful eye on manufacturing operations real-time and quickly identify and resolve line stoppages. “Trending and identification of variances, such as between shifts, also support identification of specific groups of operators that could benefit from additional training or opportunities for improving the mix of operator experience levels within shifts,” Clemens notes.

A specific example of an important development in real-time monitoring, according to Laura Choteau, quality control manager at Catalent Biologics, has been the introduction of real-time monitoring for visible particles. “Today, automation allows us to read culture plates from the start of incubation through to the end, with full traceability of the plate’s location and condition throughout. As a consequence, we can detect contamination risks much earlier and respond immediately. That reduces the likelihood of recurring contamination and helps us get much closer to identifying the root cause,” she comments.

Other notable examples of process analytical technology tools improving aseptic processing operations, according to Jean-François Boé, senior director of drug product development for Catalent Biologics, include onboard mass spectrometry and Raman spectroscopy systems embedded into compounding or fill/finish units. “The data generated from these instruments give us real-time visibility into critical process parameters. In the long term, this level of control could reduce the need for traditional final release testing, shifting more quality assurance upstream and closer to the point of manufacture,” he says.

Like Schneider, Boé emphasizes the role still played by human operators in many monitoring activities. For instance, air monitoring systems in Grade A areas still often require operators to insert culture plates, typically using glove ports. This need does carry a small but real risk of contamination, as well as the potential for plate insertion to be accidentally skipped, which would create a gap in monitoring and raises questions during batch review. These issues could be avoided, Boé says, with the use of robotics to install the plates, which would “add a layer of reliability to aseptic operations and increases confidence in the process.”

New data management software equally impactful

Automation in analytics has been around for some time and continues to improve with advances in technologies. What has driven a real shift, according to Choteau, has been how the generated data are managed and used. “Data management plays a central role in helping us act faster and make smarter decisions in aseptic environments. Modern LIMS platforms now allow us to automate calculations and perform trend analysis continuously, which provides more frequent and reliable insights, helps ensure accuracy, and allows quality teams to concentrate on investigations when abnormal trends appear,” she explains.

Off-the-shelf, user-friendly visualization and reporting software, meanwhile, has enabled engineering teams to use data in a way that would have required significant involvement of information technology personnel in the past, Clemens notes. For example, Lifecore Biomedical tracks all line interventions digitally. “Having operators identify reasons for interventions in a consistent manner from shift to shift enables our engineering teams to identify trends and take corrective actions before real issues arise,” he says.

Furthermore, both process efficiency and control are also increased. “Automation brings greater control and traceability. It minimizes sampling errors, confirms that all required samples have been taken, and provides a clear record for each action. This helps maintain compliance and strengthens confidence in our processes,” Choteau states.

Staff training, like with other aspects of digitalization and automation of aseptic processing, remains an essential component, however. Operator readiness to respond in the event of system failures must be maintained, and staff must be able to manage operations manually when needed, according to Choteau. Data security, she adds, is equally important. “Protecting data from cyber threats and ensuring its integrity remains a top priority as more systems become connected and automated,” Choteau observes.

Digital twins support effective process simulation

Modeling is an important aspect of digitalization that is benefiting many process development and manufacturing activities, including sterile production operations. Digital twin technology, for instance, is becoming increasingly valuable in drug substance manufacturing and beginning to show potential in aseptic fill/finish operations, according to Boé.

Digital twins in the pharmaceutical manufacturing context are virtual models of processes that are continuously updated with real-time data, allowing assessment of performance. “By creating a digital replica of equipment and processes, digital twins help us simulate scenarios, predict outcomes, and optimize parameters before moving to physical implementation,” he says. Boé finds this approach especially useful during process transfer, because it allows teams to anticipate risks, reduce variability, and avoid costly delays.

Artificial intelligence has growing value

Digital twins are not the only example of how automation and digitalization are being combined with artificial intelligence (AI), machine learning (ML), and other advanced computing capabilities to further improve aseptic processing. When leveraged together, these myriad technologies are accelerating timelines and enhancing process control, according to Boé.

As an example, Boé points to the benefits AI-driven models can provide for freeze-drying (lyophilization) processes. In particular, he notes they can be used to optimize cycle development, significantly reducing the time required to reach a robust process and positively impacting project timeliness and resource efficiency.

In fact, Boé expects AI and ML to play an even larger role and provide growing value as complexity—product, process, and equipment-related—continues to increase. “AI and ML help with not only data analysis and trending, failure prediction, and workflow optimization; they also support more informed decision making. All of these benefits ultimately lead to greater efficiency and reliability of aseptic manufacturing operations,” he concludes.

Reference

1. EC. Annex 1. Manufacture of Sterile Products. EudraLex–Volume 4–Good Manufacturing Practice (GMP) Guidelines. August 2023.

Article details

Pharmaceutical Tehnology®
Vol. 49, No. 8
October 2025
Pages: 18–20

Citation

When referring to this article, please cite Challener, C.A. Advances in Digitalization and Automation of Aseptic Processing. Pharmaceutical Technology 2025 49 (8).

Chip dan tag RFID | Kredit Gambar: © Albert Lozano-Nieto – stock.adobe.com

Schreiner MediPharm, unit bisnis Schreiner Group yang berbasis di Jerman, sedang meninjau opsi label baru dengan teknologi identifikasi frekuensi radio (RFID) yang akan dipamerkan perusahaan di CPHI Frankfurt 2025, yang akan diadakan pada 28-30 Oktober (1). Menurut siaran pers tanggal 8 Oktober 2025, Schreiner MediPharm mengatakan label yang diberi merek “Cap-Lock” dirancang untuk memberikan perlindungan optimal pada jarum suntik, meningkatkan digitalisasi dan efisiensi.

Bagaimana cara kerja fungsi label dan RFID?

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Klik di sini untuk semua liputan CPHI Frankfurt kami.

Referensi

1. Grup Schreiner. Cap-Lock Plus RFID: Schreiner MediPharm Mempresentasikan Solusi Keamanan Inovatif di CPHI Frankfurt 2025. Siaran Pers. 8 Oktober 2025.
2. Mirasol, F. CPHI Frankfurt Mengungkapkan Finalis Penghargaan Farmasi 2025 untuk Pengembangan Bio/Farmasi. FarmasiTech.com18 September 2025.

Kepala Manusia | Kredit Gambar: © Shpilbergstudios – Stock.adobe.com

Pada pertemuan sel dan gen 2025 di mesa, diadakan 6-8 Oktober di Phoenix, Ariz., Panelis menunjukkan bahwa akselerasi ilmiah yang cepat dalam sektor terapi sel dan gen (CGT) yang menghasilkan data klinis transformatif yang terjadi pada kanker baru (EG, glioblastoma, ovaria) dan non-cancer indikasi.

Para pemimpin industri berkumpul selama sesi berjudul “Standar Baru untuk Pabrikan CGT: Fleksibilitas dan Skalabilitas” pada 6 Oktober untuk mengatasi hambatan ini, dengan alasan bahwa industri harus beralih ke paradigma baru – berlabel CGT 2.0 – yang memberikan fleksibilitas dan skalabilitas secara bersamaan (1).

Dipimpin oleh Jason Foster, CEO dan direktur eksekutif Ori Biotech, panel menekankan bahwa pertukaran tradisional antara mempertahankan fleksibilitas proses untuk pengembangan tahap awal dan perencanaan kelayakan komersial skala besar tidak lagi berkelanjutan.

“Idenya adalah untuk memberikan fleksibilitas dan skalabilitas pada saat yang sama, dan kita akan berbicara tentang bagaimana kita melakukan itu; dan itu benar -benar merupakan ciri khas dari apa yang saya sebut CGT 2.0,” kata Foster pada awal diskusi panel (1).

Apa yang mendefinisikan kembali kesuksesan komersial?

Untuk industri biofarmasi, keberhasilan dalam CGT tidak dapat lagi didefinisikan semata -mata oleh kemanjuran klinis, diskusi panel mengungkapkan. Ken Harris, Kepala Petugas Strategi dan Kepala Kecerdasan Buatan (AI) di Omniabio, menekankan perlunya pendekatan “bekerja mundur”, di mana keadaan akhir ditentukan oleh akses dan keterjangkauan pasien yang meluas. Pendekatan ini berarti bahwa manufaktur harus layak tidak hanya di Pusat Medis Akademik Besar (AMC), seperti City of Hope yang berbasis di California atau Rumah Sakit Anak Philadelphia (CHOP), tetapi disampaikan dalam pengaturan rumah sakit komunitas.

“Jika Anda meminta 90% orang di industri ini apa keadaan akhir mereka, itu adalah produk yang efektif dan aman secara klinis,” kata Harris selama panel. “Itu salah satu pilar, tapi itu bukan satu -satunya pilar.”

Sementara itu, mengabaikan kimia, manufaktur, dan kontrol (CMC) sejak awal hasil dalam produk yang tidak dapat hidup, menekankan Taby Ahsan, PhD, Wakil Presiden, Operasi Terapi Sel dan Gen, Kota Harapan. Ahsan mengkonfirmasi bahwa uji tuntas oleh mitra potensial semakin fokus pada viabilitas manufaktur, menjadikan CMC sebagai “Dealbreaker” bahkan ketika data klinis menjanjikan. “Data klinis, atau bahkan data hewan, akan membawa (mitra) ke meja, tetapi, semakin banyak, uji tuntas mereka sangat fokus pada CMC, dan itu berubah menjadi pemutus kesepakatan,” katanya.

Apa yang dibawa oleh proses platform dan sistem modular ke meja?

Untuk mengaktifkan fleksibilitas, AMC, seperti City of Hope, memanfaatkan proses platform – unit modular yang sudah diperiksa dan dapat mendukung beberapa aplikasi obat baru yang diselidiki (IND) dengan cepat. Misalnya, City of Hope menggunakan beberapa platform untuk mendukung 18 Inds, Ahsan menunjukkan.

Tom Wilton, Wakil Presiden Senior, Inovasi Usaha, Rumah Sakit Anak Philadelphia (CHOP), juga menyoroti gagasan bahwa fleksibilitas di masa depan memerlukan penentu sistem modular dan interoperable yang kompatibel dengan berbagai jenis sel, sistem pengiriman, dan muatan, termasuk pekerjaan sel induk, sel reseptor antigen chimeric (CAR-T), dan gen gen yang dipersonalisasi. “Selama 10 tahun terakhir, itu benar -benar … pusat medis akademik yang telah mengembangkan proses ini pada awalnya,” kata Wilton.

Strategi apa yang dapat digunakan untuk mengurangi variabilitas produk akhir?

Rintangan utama untuk skala manufaktur CGT adalah variabilitas proses. Bahkan operator manusia yang sangat terlatih selalu memperkenalkan variasi yang tidak dapat ditangkap oleh catatan batch, kata Andrew Snowden, PhD, direktur senior, pengembangan terapi sel alogenik dan autologous, Johnson & Johnson Innovative Medicine, di panel. Faktor manusia ini membuat otomatisasi penting untuk reproduktifitas dan skalabilitas yang cepat, Snowden menunjukkan.

Otomatisasi sederhana dalam proses manual dianggap “buah gantung rendah” untuk meningkatkan kualitas dan mengurangi biaya, komentar Snowden. “(Seseorang akan) melihat jumlah variabilitas yang luar biasa karena seluk -beluk eksekusi yang tidak pernah dapat dimasukkan ke dalam catatan batch atau pelatihan tanpa mereka berubah menjadi dokumen berukuran baru,” jelasnya.

Selain itu, industri menderita kesenjangan data yang signifikan karena sering gagal menganalisis atau berbagi data yang dikumpulkan. Harris menjelaskan bahwa Omniabio, dalam menangani kesenjangan data ini, menggunakan platform AI sederhana untuk menganalisis langkah -langkah tenaga kerja dan proses dalam operasi mereka dan mengidentifikasi penghematan biaya 27% dalam persalinan, menggarisbawahi dampak keuangan langsung dari pengungkitan analitik dasar. Tujuan utamanya adalah kontrol adaptif, di mana sistem menggunakan pembelajaran mesin untuk memandu keputusan manufaktur real-time, kata Harris.

Apa manfaat membangun ekosistem CGT kolaboratif?

Panelis menyimpulkan bahwa mencapai CGT 2.0 membutuhkan “pergeseran mentalitas” yang mendalam dari melihat pengembangan sebagai upaya penelitian untuk memperlakukannya sebagai program komersialisasi. Kolaborasi sangat penting untuk menghilangkan transfer teknologi yang memakan waktu, yang saat ini dapat memakan waktu 12 hingga 24 bulan, para panelis mendiskusikan.

AMC, misalnya, harus bermitra dengan penyedia teknologi untuk menawarkan lingkungan “kotak pasir” untuk iterasi yang cepat dan peningkatan platform manufaktur baru, memastikan mereka cocok di semua populasi pasien. Para panelis sepakat bahwa pemain industri harus berkumpul dan memprioritaskan apa yang menguntungkan bidang keseluruhan, daripada organisasi individu, yang memerlukan mempromosikan berbagi data dan interoperabilitas. Dengan cara ini, seluruh sektor CGT dapat bergerak menuju pertumbuhan eksponensial dan akses pasien yang luas. Penghapusan kemacetan, diidentifikasi lebih awal melalui prinsip -prinsip seperti Kaizen (2) atau teori kendala (3), dan mengoptimalkan logistik “mil terakhir” (pengiriman produk ke pasien) juga penting untuk menurunkan biaya barang yang terus -menerus tinggi.

Klik di sini untuk liputan konferensi lainnya.

Referensi

1. Pertemuan sel dan gen di mesa. Standar baru untuk pembuatan CGT: fleksibilitas dan skalabilitas. Presentasi di Cell and Gene Meeting di Mesa, 6 Oktober 2025. https://meetingonthemesa.com/agenda/
2. Abuzied, Y. Panduan praktis untuk pendekatan Kaizen sebagai alat peningkatan kualitas. Glob J Qual Saf Healthc. 2022, 5 (3), 79–81. Doi: 10.36401/jqsh-22-11
3. Teori Institut Kendala. Teori Kendala (TOC) dari Dr. Eliyahu Goldratt. tocinstitute.org (Diakses 6 Oktober 2025).

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