New FDA guidance spells out which drugs require risk management plans – Endpoints News

As the ma­jor­i­ty of drug short­ages are still as­so­ci­at­ed with man­u­fac­tur­ing-re­lat­ed qual­i­ty is­sues, the FDA on Thurs­day pub­lished new draft guid­ance spelling out how to proac­tive­ly as­sess risks to man­u­fac­tur­ing process­es and sup­ply chains, while un­der­stand­ing the mar­ket’s vul­ner­a­bil­i­ties.

While drug short­ages peaked in 2011, the FDA says in its new 18-page draft guid­ance that the num­ber of new drug short­ages “has de­clined sig­nif­i­cant­ly since” that peak, reach­ing a low in 2015 and 2016, thanks in part to a new law’s en­act­ment, known as FDA­SIA, which helped the agency bet­ter pre­vent or mit­i­gate drug sup­ply dis­rup­tions and short­ages, and clar­i­fied cGMP re­quire­ments.

How­ev­er, the FDA ex­plains how this down­ward trend “did not con­tin­ue in sub­se­quent years,” not­ing:

Drug short­ages con­tin­ue to oc­cur and at rough­ly the same lev­els since 2018. Fur­ther, drug short­ages have grown more per­sis­tent (i.e., in­creased length of ac­tive drug short­ages). Many of the rea­sons for drug short­ages are, for ex­am­ple, is­sues re­lat­ed to drug qual­i­ty, dis­rup­tions to sup­ply chain man­u­fac­tur­ing op­er­a­tions (e.g., caused by nat­ur­al dis­as­ter or dis­con­tin­u­a­tion of com­po­nents by sup­pli­ers), lim­i­ta­tions in fore­cast­ing fu­ture de­mand, and mar­ket with­drawals of drug prod­ucts.

In March 2020, with the en­act­ment of the CARES Act, Con­gress added a sec­tion to the law gov­ern­ing the FDA, which took ef­fect in Sep­tem­ber 2020, and that re­quires cer­tain man­u­fac­tur­ers to de­vel­op, main­tain, and im­ple­ment a “re­dun­dan­cy risk man­age­ment plan that iden­ti­fies and eval­u­ates risks to the sup­ply of the drug, as ap­plic­a­ble, for each es­tab­lish­ment in which such drug or ac­tive phar­ma­ceu­ti­cal in­gre­di­ent of such drug is man­u­fac­tured.”

Since at least the pub­li­ca­tion of ICH Q9 in 2006, the phar­ma­ceu­ti­cal in­dus­try has tak­en steps to im­ple­ment qual­i­ty risk man­age­ment prin­ci­ples.

The types of drugs for which the FDA will re­quire risk man­age­ment plans in­clude:

• Life-sus­tain­ing and life-sup­port­ing drugs and APIs
• Drugs to pre­vent or treat a de­bil­i­tat­ing dis­ease or con­di­tion, in­clud­ing for emer­gency med­ical care or surgery or that’s crit­i­cal to the pub­lic health dur­ing a pub­lic health emer­gency
• Any as­so­ci­at­ed med­ical de­vice used for the prepa­ra­tion or ad­min­is­tra­tion of these drugs

For 7 oth­er types of drugs, the FDA draft says that it rec­om­mends, rather than re­quires, RMPs:

1. Drugs to treat rare dis­eases
2. Drugs that lack ap­pro­pri­ate al­ter­na­tives
3. Med­ical coun­ter­mea­sures used in the event of a po­ten­tial pub­lic health emer­gency stem­ming from a ter­ror­ist at­tack with a bi­o­log­i­cal, chem­i­cal, or ra­di­o­log­i­cal/nu­clear ma­te­r­i­al, or a nat­u­ral­ly oc­cur­ring emerg­ing dis­ease and oth­er threat agents (i.e., es­sen­tial to na­tion­al se­cu­ri­ty)
4. Sole source drugs
5. Drugs with on­ly one API man­u­fac­tur­er in the prod­uct’s sup­ply chain that has been ap­pro­pri­ate­ly qual­i­fied by the qual­i­ty unit of the fin­ished dosage form (FDF) es­tab­lish­ment
6. Drugs with on­ly one FDF man­u­fac­tur­er in the prod­uct’s sup­ply chain
7. Drugs man­u­fac­tured in a fa­cil­i­ty (in­clud­ing pack­ag­ing fa­cil­i­ties and lab­o­ra­to­ries) with an in­spec­tion in the last 5 years that was clas­si­fied as of­fi­cial ac­tion in­di­cat­ed (OAI) and there is no oth­er man­u­fac­tur­ing fa­cil­i­ty that is qual­i­fied in the prod­uct’s sup­ply chain to con­duct that op­er­a­tion

While the agency ac­knowl­edges that short­ages and short­age mit­i­ga­tion ef­forts pose a sig­nif­i­cant fi­nan­cial and re­source bur­den on phar­ma com­pa­nies, among oth­er stake­hold­ers, the FDA said it views RMPs as an im­por­tant mech­a­nism to proac­tive­ly iden­ti­fy, as­sess, and mit­i­gate the risks that might lead to a dis­rup­tion in the sup­ply of drugs.

Ad­di­tion­al­ly, in re­cent years, FDA said it has ob­served a rise in num­ber of cy­ber­at­tacks on drug man­u­fac­tur­ers “and is in­creas­ing­ly con­cerned about the ef­fect of such at­tacks on the drug sup­ply chain.”

In 2017, a cy­ber­at­tack in­volv­ing ran­somware on Mer­ck’s man­u­fac­tur­ing ops led to is­sues that last­ed for more than a month af­ter the at­tack oc­curred.