Marketing requirements, biopharmaceuticals

Pharmaceutical excipients available on the market seem sufficient to support typical oral solid dosage form development. In some cases, new chug candidates have physicochemical and biopharmaceutical properties that are less than ideal. These chugs present formulation challenges and may require either the discovery of new excipients or improvement of existing excipients. From a regulatory perspective, there is no answer for the question of registration of an excipient as a separate entity. 

Even on their own these are profound issues in the development of any product, but they have very particular implications for the difficult processes of formal pharmaceutical development, clinical trial, and marketing authorization of the full range of biopharmaceuticals. The answers will define major features of how the experimental work is done and the resources required to do it. 

Arindam Bose (Pfizer Central Research) further discussed the ICH documents and presented a rationale for the recommended combination of test procedures and process clearance validations required to demonstrate that marketed biopharmaceuticals are free of adventitious agents. He showed that testing of Pre-Seed Stock (PSS), the Master Cell Bank (MCB), and the Working Cell Bank (WCB) is required to demonstrate that they are free from contamination by mycoplasma, bacteria, molds, and yeasts. In addition, viral clearance validation studies must be performed on scaled down versions of each chromatographic step and the viral inactivation/removal step employed in the product purification scheme. Finally, clearance studies must be conducted with a panel of relevant and model viruses (typically three to four) to establish that the purification scheme will indeed purge any viruses that may be inadvertently introduced during processing. 

It is almost impossible to comment on the average time that a biopharmaceutical product needs to progress from laboratory bench to market. For a MAb, from discovery to FDA approval and commercial launch, it costs about US 800 million, and takes 12-15 years [10]. However, a recent FDA whitepaper reported that the required investment for one successful drug launch (discovery through launch) is US 1.7 billion [12]. In addition, one must be aware of the fact that only one in 5000 candidates will make it all the way to commercial success. 

Projecting market demand for specific classes of therapeutics in development will remain a major planning issue for bio-pharmaceutical companies. The ability to meet the demand for biopharmaceutical production capacity, whether through in-house manufacturing or outsourced contract manufacturing, carries strategic and financial implications. Also, FDA approval policy and the development of the biogenerics market will have a major impact on future capacity requirements (see Part VII, Chapter 4). 

Analytical methods are also required to characterize biopharmaceuticals in vivo. Pharmacokinetics deals with the description of the fate of a pharmacologically active compound in the biosystem. This can either be animals in the early development and is complementary to pharmacological and toxicological studies (predominantly rats, mice, rabbits, dogs or monkeys), or human volunteers or patients during clinical development and post-marketing. 

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