Felicity Thomas is Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Felicity Thomas

Oral solid dosage (OSD) forms are commonplace within the pharmaceutical industry thanks to several advantages such a form can offer, including convenience of manufacture, ease of administration, and cost-effectiveness. According to market research, the OSD market outlook is favourable and expected to experience continued growth, driven by the low production cost—particularly within developing nations (1).

The manufacture of all pharmaceutical finished dosage forms, including OSD, must adhere to regulatory guidance and specifications to ensure quality and safety of the products are maximized. Current good manufacturing practices (CGMPs), for example, are the minimum standards that must be met and require a proactive quality approach be taken to the manufacture of finished products so that any risks, such as contamination, are minimized or eliminated (2).

CGMP requirements tend to be general and allow for manufacturers to implement quality controls on an individual basis. “The general expectations for CGMP, relating to OSD forms, revolve around ensuring consistent and acceptable product quality and safety,” confirms Dave DiProspero, senior fellow, Pharmaceutical Process, CRB. “This [practice] follows the traditional five Ps of GMP: people, premises, processes, products, and procedures. Regulatory guidance and good practices are based on these five Ps and focus on protecting the product from contamination and preventing any mix ups. Operations must be fully understood and in control.”

OSD regulatory guidance has been relatively current for many years, explains DiProspero, which is contrary to other areas of manufacturing, such as the sterile environment, where recent updates have been made via documents like Annex 1. “The US Food and Drug Administration (FDA) has issued various technical guidance documents [for OSD forms], most recently around continuous manufacturing; however, the most typical industry guidance is related to ISPE [International Society for Pharmaceutical Engineering Operations] OSD Baseline Guide Volume 2 and ISPE Good Practice Guide Continuous Manufacturing of OSD Forms” (3,4).

Within Europe, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted updated manufacturing guidelines for finished dosage forms in 2017 (5). These updated guidelines addressed legislative requirements and followed the format of the common technical document (CTD) module 3 dossier. Additionally, the changes to manufacturing practices as related to the global, complex supply chains were reflected.

Although no major changes are expected to be made to GMP guidance for OSDs in the near future, DiProspero does point out that regulators are focusing more heavily on manufacturers of nutraceuticals and dietary supplements. “More guidance and closer alignment with [prescription] products are likely to occur in the years ahead,” he says. “Many of the major dietary supplement manufacturers are already greatly improving their facilities and processes to align with pharma facilities.”

“Continuous manufacturing has been the leading new processing platform paving its way in the development of new OSD products and conversion from traditional batch products,” notes DiProspero. It is known that regulatory authorities around the world have proactively supported the use of innovative manufacturing approaches, such as continuous manufacturing (6). “FDA have reacted very positively and strongly in advocating this platform and providing guidance on its use and implementation,” DiProspero confirms.

Recently, there has been greater harmonization around the regulation of continuous manufacturing, DiProspero continues. “The 2022 ISPE Continuous Manufacturing Good Practice Guide was heavily based on establishing a set of minimum equipment requirements for each type of system to function as a part of an integrated process train, making it easier for manufacturers and equipment suppliers to identify and define minimum attributes,” he says. “The March 2023 FDA guidance for industry (Q13 

Continuous Manufacturing of Drug Substances and Drug Products

) describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing” (7).

“[Further,] FDA’s guidance builds on existing International Council for Harmonisation (ICH) quality guidance (Q13), providing clarification on continuous manufacturing concepts and describing scientific approaches and regulatory considerations specific to continuous manufacturing of drug substances and drug products,” DiProspero adds (8).

Ensuring compliance and quality in modern practices

Currently, to ensure compliance and improved quality of modern finished products, companies are working on improved process containment and closed or integrated systems, DiProspero highlights. “It has always been common to contain and close when dealing with hazardous/potent compounds, but [there are now] improved systems and operations for non-potent and non-hazardous,” he remarks. “Minimizing dust, controlling feed, and improving ergonomics and operator safety are among some of the most common best practices being seen in modern powder handling and OSD manufacturing operations.”

Baseline Guide Vol. 2: Oral Solid Dosage Forms 3rd Edition

. Guidance Document, November 2016.
4. ISPE. 

Good Manufacturing Practice Guide: Continuous Manufacturing of Oral Solid Dosage Forms

. Guidance Document, March 2022.
5. EMA. 

Guideline on Manufacture of the Finished Dosage Form

. Guidance Document, July 2017.
6. Wahlich, J. Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms. 

Q13 Continuous Manufacturing of Drug Substances and Drug Products

. Guidance for Industry, March 2023.
8. ICH. Q13, 

Felicity Thomas is the European/senior editor for Pharmaceutical Technology Group.


Vol. 35, No. 8
August 2023
Pages: 32–33

When referring to this article, please cite it as Thomas, F. Ensuring OSD Quality and Safety. 

Articles

Current good manufacturing practices for oral solid dosage forms protect the product from contamination and potential errors.

Ensuring OSD Quality and Safety

As Europe experiences extreme weather conditions—with sweltering temperatures in Southern areas, wildfires destroying parts of the Greek islands, and deadly storms affecting other parts of the region—it is becoming clear that more action needs to be taken to tackle climate change. For the pharmaceutical industry, tackling climate change is not just about cutting emissions but also about combatting the adverse effects on health that are linked to the warming world.

In 2021, the World Health Organization (WHO) reported that “climate change is the single biggest health threat facing humanity” and predicted that, between 2030 and 2050, it will cause approximately 250,000 extra deaths per year (1). Shortly after WHO’s report, during the United Nations Climate Change Conference of the Parties (COP26), held between 31 Oct. and 13 Nov. 2021, a public-private partnership—the Sustainable Markets Initiative (SMI) Health Systems Task Force—was launched, aimed at speeding up the delivery of net zero healthcare (2).

Members of the Task Force, who include CEOs of large biopharmaceutical companies and public bodies, collaborated on industry commitments that will help support the transition to sustainable healthcare. A year later, during the COP27 meeting in 2022, the Task Force set out some core commitments, actions, and recommendations for industry that focused on three priority areas—“supply chain, patient care pathways decarbonization, and the use of digital innovation in clinical research” (2).

The joint action of the members involved in the Task Force has continued with a further scaling up of targets for suppliers in the industry to try and reach a net zero target. Most recently, Task Force members published an open letter stressing the criticality of action on climate change within the industry, which laid out minimum supplier targets for climate and sustainability across the value chain (3).

Ultimately, climate change is already impacting global health negatively and only a significant collaborative effort is going to reduce that effect. As the Task Force members wrote, “Healthcare supply chains must become greener, more efficient, and circular … Shifting to net zero, climate resilient health systems cannot be achieved in siloes. We must collaborate, across the sector and across borders, to secure a healthier tomorrow” (3).

Open Letter on Supplier Targets from Members of the Sustainable Markets Initiative Health Systems Task Force

When referring to this article, please cite it as Thomas, F. A Healthier Tomorrow? 

Only a significant joint effort across the supply chain will help to make healthcare more sustainable and reduce the impact of climate change on global health.  

A Healthier Tomorrow?

In this episode of the Drug Solutions podcast, Felicity Thomas, European/Senior Editor, talks to David Tisi, technical director at Senopsys LLC, and Reenal Gandhi, global business development director for the Prescription Division of 

. In the first segment of the episode, David chats about some of the key challenges impacting oral dosage forms and the approaches and solutions available that are helping developers overcome these hurdles. After, Reenal details the intricacies of intranasal drug dosage forms, such as the convenience and the growth of this route of administration, challenges of development, and the possibilities of repositioning drug products.

David Tisi, technical director at Senopsys LLC

David is founding member of the scientific team at Senopsys LLC, a specialty services firm dedicated to the development of palatable drug products. He has over 15 years of experience in taste assessment and taste masking novel drug formulations for children and adults, leveraging his background in sensory science and food chemistry. David received his Masters in Food Science from Cornell University and began his career in product innovation at PepsiCo and Nestle.

Reenal Gandhi, global business development director for the Prescription Division of 

Reenal has more than 15 years’ experience within the drug delivery and pharmaceutical industries, involved in the development and commercialization of wide-ranging drug delivery solutions. Over the course of her career, Reenal has actively worked on business development related to nasal and injectable devices, such as prefilled syringes and autoinjectors. Since December 2020, Reenal has been working for Aptar Pharma, driving the assessment of new opportunities and focusing on new technologies in particular.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

Podcasts

In this episode, David Tisi and Reenal Gandhi provide expert insights into advances and innovations changing the drug dosage form landscape.

Drug Solutions Podcast: Innovations and Advances in Drug Dosage Forms

In this episode of the Drug Solutions podcast, Felicity Thomas, European/Senior Editor, chats with Sergey Vlasenko, associate vice-president, Pharma/Biopharma, Agilent, about trends impacting bio/pharmaceutical manufacturing. Sergey provides an overview of some of the key trends and then focuses on a novel modality—oligonucleotides—highlighting the specific challenges related to the manufacture of these exciting therapeutics.

Sergey Vlasenko, associate vice-president, Pharma/Biopharma, Agilent

Vlasenko joined Agilent in 2018 through its acquisition of the privately owned company ProZyme, a developer and manufacturer of glycan reagents, kits, and standards, required for biotherapeutic protein characterization. Prior to ProZyme, Vlasenko managed the R&D and marketing teams developing and commercializing innovative products for the Pharma and Biopharma industry.

In this episode, Sergey Vlasenko from Agilent chats about bio/pharmaceutical manufacturing trends, with a particular focus on oligonucleotides.

Drug Solutions Podcast: Unlocking the Latest Manufacturing Trends

Meletios Therapeutics, a French biotech company focused on the R&D of next-generation antiviral treatments, has been awarded with funding worth €1.2 million (US$1.3 million) from Bpifrance’s Deeptech development program to aid in its work.

According to a June 29, 2023 press release, the monies granted to Meletios Therapeutics will be used to validate the company’s Defective Viral Genome (DVG) platform and to develop the first candidates from this platform until they are suitable for entry into clinical phases. It was this technology that was deemed to meet the criteria set out by Bpifrance to discern whether a company can be classified as Deeptech—one that is closely linked to the world of research and that proposes a disruptive innovation compared with existing technologies.

The DVG platform, which originated from the Pasteur Institute and has been developed by Meletios Therapeutics, generates, identifies, and uses DVGs—truncated copies of a virus that have lost their pathogenic properties. In February 2022, Meletios Therapeutics obtained authorization from the Pasteur Institute to extend the exclusive license for the platform, allowing Meletios Therapeutics to apply a highly specific method of generating new DVGs to the entire family of flaviviruses, alphaviruses, and coronaviruses.

“One of our main challenges in the development of this new generation of treatments was to develop a safe, effective, and, above all, rapid method for the identification and supply of DVGs in the context of viral epidemics. Viruses are indeed capable of spreading very quickly in the population, and this is all the truer in the case of new emerging viruses whose properties are not yet fully known. Therefore, there is a real challenge to develop and make available to clinicians a rapid and effective therapeutic response to these infections,” said Catherine Martre, CEO of Meletios Therapeutics, in the press release. “We are delighted to receive this funding, which demonstrates the scientific relevance of our technology and the confidence place in us by Bpifrance. With this new financial support and its disruptive technology platform, developed together with the Pasteur Institute, […] Meletios Therapeutics is now fully equipped to enter the next phases of the development of its lead drug candidates.”

Meletios Therapeutics has been awarded with funding worth €1.2 million (US$1.3 million) from Bpifrance’s Deeptech development program.

Meletios Therapeutics’ Efforts in Antiviral Field Gains Recognition from Bpifrance

Integrated research, development, and manufacturing services company, Syngene, has acquired a multi-modal facility in Bangalore, India, from Stelis Biopharma, it was announced in a July 4, 2023 press release. The acquisition provides Syngene with an extra 20,000 L of installed biologics drug substance manufacturing capacity.

Originally built to manufacture COVID-19 vaccines, the acquired facility will now be repurposed and revalidated for the manufacture of monoclonal antibodies by Syngene. Additionally, the site, which includes a commercial-scale, high speed, fill/finish unit, has the potential for future expansion of a further 20,000 L capacity.

“This acquisition strengthens our growing position as a leading biologics contract development and manufacturing service provider and adds drug substance capacity and a drug product capability years earlier than our internal capex program,” said Jonathan Hunt, managing director and CEO of Syngene, in the press release. “We see healthy demand for high-quality biologics manufacturing capacity from sectors ranging from large pharma to emerging biotech companies.”

The transaction for the facility cost INR 702 Crores ($86 million) and has been approved by both companies’ boards of directors. Closure of the transaction is expected within 90 days, as long as the customary conditions are met.

Syngene has acquired a multi-modal biologics drug substance manufacturing facility in Bangalore, India, from Stelis Biopharma.