BIOPHARMACEUTICAL MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 344

addressed by including multiple lots in product qualification exercises and by
periodically testing incoming lots of material.
12.3.7 Primary Packaging
12.3.7.1 Process Overview Packaging for biopharmaceuticals is a major area
of concern primarily because of its impact on product quality. The FDA's require-
ment, as spelled out in the “Guidance Container Closure Systems for Packaging
Human Drugs and Biologics,” provides companies with the guidelines as to what
is expected from them to demonstrate that the proposed package and its com-
ponents are suitable for their intended use and will maintain the quality, safety,
potency, and stability of the drug product over its intended shelf life. In addition
to maintaining product quality, primary packaging for biotechnology drug sub-
stances also need to be sterile, scalable, disposable, and readily available. There
are three important points to consider when choosing primary packaging:
1. Does the container-closure system protect the product from environmental
challenges (e.g., moisture, light, oxygen, shipping)?
2. Is the dosage form identified in the FDA guidance as a high risk for pack-
aging concerns (e.g., inhalation or injectable drug)?
3. Does the container-closure system play a functional role in the delivery of
the drug product (e.g., inhalations and transdermals)?
An affirmative response to these questions indicates that the primary packag-
ing could significantly impact the product and the information supplied to the
agencies will undergo careful scrutiny in the license applications.
Drug Substance Typically, after the final purification step, bulk drug substance
is formulated, filtered, and stored under defined conditions in either plastic bottles
or bioprocessing containers (e.g., ethylene vinyl acetate or EVA bags), or glass
containers (e.g., tetrafluoroethylene or Teflon glass bottles), or in stainless steel
vessels. There is no single packaging configuration that is suitable for all products;
they all have advantages and disadvantages (e.g., the glass bottle containers are
inert but fragile), so the selection of the correct primary packaging depends upon
the unique product/process characteristics and the business needs of the sponsor.
Drug Product For biotechnology-derived drug products, parenteral or intra-
venous (IV) injections of proteins often provide the most efficient route of
delivery for protein-based formulations. Despite the significant advances in deliv-
ering therapeutic enzymes, peptides, and proteins through nontraditional means,
injection remains the principal delivery system. The typical primary packaging
presentations used for protein drug products are single-dose vials, IV bags, or pre-
filled syringes. The product is provided either as a solution, or, as a lyophilized
cake, which is reconstituted and injected via syringe. Requirements for prod-
uct purity, activity, and shelf life are critical and necessitate high standards