What a combination
Pharmaceutical CDMOs will need to address the requirements of unfamiliar products if they are to compete in combination products . We report from a recent Alcami webinar
Combination products are becoming increasingly important to pharmaceutical CDMOs like Alcami , said Jacque Uribe , VP of quality operations , who was speaking at a recent company webinar . Alcami has developed its own internal implementation programme reflecting this . In September 2009 , Uribe noted , the FDA published a proposed rule ( 74 FR 48423 ). This was the first part of its still ongoing effort to improve the consistency of , and aid industry in , implementing the regulatory requirements for combination products . The final rule , 21 CFR Part 4 , cGMP for Combination Products , became
Figure 1 – Options within streamlined approach effective in 2013 . A final guidance document , ‘ cGMP Requirements for Combination Products ’ was released in 2017 . Under 21 CFR Part 3.2 ( e ), a combination product is defined as a product comprised of two or three of the regulated components of ‘ drug ’, ‘ device ’ and ‘ biological product ’. These three terms are defined under FD & C Act ( 21 USC 321 ( g ) and ( h )) and Section 351 ( i ) of the PHS Act ( 42 USC 262 ( i )) respectively . One important element of these definitions relevant to combination products , Uribe noted , is that a device “ does not achieve its primary intended purposes through chemical action ” in the body and “ is not dependent upon being metabolised for the achievement of its primary intended purposes ”.
Combinations of two drugs , two devices , two biologics or combinations of all three with a food or cosmetic product are not considered to be combination products . Within the category of ‘ combination products ’ are :
• ‘ Single Entity Combination Products ’, which are physically , chemically , or otherwise combined or mixed and produced as a single entity
• ‘ Co-Packaged Combination Products ’, where two or more separate products are or packaged together in a single package or as a unit , such as a first aid kit
• ‘ Cross-Labelled Combination Products ’, which are a drug or product packaged separately and intended for use only with an approved , individually specified
If the operaVng manufacturing control system is Part 820 ( QS RegulaVon )
If the operaVng manufacturing control system is Part 210 / 211 ( CGMP RegulaVon )
CGMP Requirements |
Title |
Carefully consider these epecific QS requirements |
Title |
§ 211.84 |
Tes5ng & approval or rejec5on of components , drug product containers & closures |
§ 820.20 |
Management responsibili5es |
§ 211.103 Calcula5on of yield § 820.30 Design controls
§ 211.132
Tamper-evident packaging requirements for over-the-counter human drug products
§ 820.50 Purchasing controls
§ 211.137 Expira5on da5ng § 820.100 Correc5ve & preventa5ve ac5ons
211.165 Tes5ng and release for distribu5on
§ 820.170
Installa5on
§ 211.166 Stability tes5ng § 820.200 Servicing § 211.167 Special tes5ng requirements § 211.170 Reserve samples
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