Biologics Regulation and ResearchThe People and Work of Buildings 29 & 29A

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Recalls are an important part of regulating biological products. Some are initiated by the company, ; others proceed from FDA’s request. The Bureau of Biologics took part in its first biologics recall in FDA in 1973 , when a Philadelphia firm issued a voluntary recall for immune serum globulin that was distributed in vials containing 25 percent less product than labeled. After the transfer to FDA, the Bureau utilized a new enforcement approach to violative biologics, employing FDA-supervised voluntary recalls. Their employment resulted in non-sterile serum albumin linked to multiple cases of septicemia, hypo-potent HAA, misbranded bacterial antigen, and other unlawful biological products being efficiently and thoroughly taken out of distribution and followed up by the agency. 

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The agency issued over 300 Regulatory Letters to establishments in 1974—mostly to blood facilities.  These These official letters identify violations and indicate a deadline for correction before the party is subject to court proceedings. The Bureau of Biologics also obtained a decree for the destruction of improperly stored lots of influenza vaccine and tetanus toxoid and secured a permanent injunction against multiple facilities of a Florida plasmapheresis firm in major and repetitive violation of regulations for the collection and processing of plasma. Two years later FDA obtained the first permanent injunction against an intrastate blood bank, which enjoined it from operating in violation of the Federal Food, Drug, and Cosmetic Act.   Inspections at an Ohio hospital blood bank on two occasions revealed serious deficiencies which threatened both blood donors and recipients, and each visit prompted increasingly severe warnings if non-compliance with regulations continued. After a third inspection revealed ongoing and hazardous operations outside of the regulations, the agency secured the permanent injunction, which allowed the hospital to operate only in emergency situations and to receive blood from outside sources.    

Adverse event reporting has had a checkered history across all FDA medical product centers.  In In October 1994 CBER amended the biologics regulations to require that manufacturers of licensed biological products must report to FDA, within 15 working days, all serious and unexpected adverse events relating to their products; any significant increase in the frequency of serious but expected reactions; periodically, all other adverse experiences; and biologic distribution information.

Regulation of the biologics marketplace can take many different forms and must be equipped to pivot quickly to address countless threats to public health. For example, Congress appropriated $300,000 for FDA to hire 48 temporary investigators to help prevent the diversion of DBS-cleared lots of licensed Salk polio vaccine from legitimate distribution channels—those used by the six producers to ship vaccine to the states and then to public and private distributors.  FDA FDA provided the training, oversight, and on-site assistance for the temporary staff. Though unclear how long this program would last, the agency did not encounter any missing vaccine.  A A case from 2003 illustrated another turn the regulation of biologics could take. FDA’s Office of Criminal Investigations, established only shortly before, announced the discovery of counterfeit Procrit (epoiten alfa) in the marketplace. Some samples were contaminated with bacteria, and FDA laboratories found others completely lacking in active ingredient. Both the manufacturer and FDA alerted healthcare providers and patients as well to the problem and the lot numbers in question. Four months later Criminal Investigations announced three convictions in this case, though it was unclear if patients had been injured by the counterfeit product.

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