The US Food and Drug Administration (FDA) will host a two-day public advisory committee meeting on 27 and 28 October to look into updating a list of bulk drug substances that should not be compounded, and another list of substances that can be compounded.
The Drug Quality and Security Act (DQSA) of 2013 was passed in the wake of a deadly outbreak of fungal meningitis caused by deficient compounding practices at a Massachusetts-based company.
Historically, compounding pharmacies were regulated by state boards of pharmacy, but after the meningitis outbreak, legislators updated the standards by which pharmaceutical compounding is regulated by FDA.
The legislation creates a voluntary registration system by which compounding facilities can sign up to be inspected by FDA and declared as “outsourcing facilities.”
But the legislation also bans compounders from making “essentially a copy of a marketed and approved drug.” Most recently, FDA issued a Form 483 to an outsourcing facility in Arizona because of some sterility concerns.
The legislation also mandates that FDA establish a list of drugs that are “reasonably likely to lead to an adverse effect on the safety or effectiveness of the drug of category of drugs,” and another list of substances that can be compounded.
In the morning session of 27 October, the Pharmacy Compounding Advisory Committee will discuss a revision to this list of drug products that may not be compounded because of safety or effectiveness concerns.
FDA now is considering whether to amend that list of drug products to include those containing quinacrine for intrauterine administration.
According to FDA, quinacrine hydrochloride (QH) tablets were originally marketed in the US in the early 1930s for the treatment of malaria. In 1964, an injectable form of quinacrine was approved for the treatment of recurrent ascites associated with several types of cancer. However, marketing of both of these products was subsequently discontinued.
In addition, two studies under an investigational new drug (IND) application for QH, which was later canceled, raised concerns about the drug’s mutagenicity, long-term safety and possible carcinogenicity.
Later on 27 October, the committee will discuss six bulk drug substances nominated for inclusion on the section 503A bulk drug substances list, which includes substances that can be compounded.
FDA intends to discuss: Quinacrine hydrochloride, methylsulfonylmethane (MSM), curcumin, germanium sesquioxide, rubidium chloride, and deoxy-D-glucose.
And on 28 October, during both the morning and afternoon sessions, the committee will discuss four other bulk drug substances nominated for inclusion on the 503A list: AlanylL-glutamine, glutaraldehyde, glycyrrhizin, and domperidone.
Breakdown of Previous FDA Actions
FDA has previously issued warning letters and safety alerts to companies attempting to market a number of these nominated drug substances as treatments for an assortment of diseases and conditions, though some have also been recognized as safe by the agency.
In a letter to Sabinsa Corporation in 2013, FDA said that curcuminoids (curcumin is the principal curcuminoid found in turmeric) is generally recognized as safe (GRAS) for use in food, though the agency also sent a warning letter to a company purporting to sell curcumin as a cancer treatment.
As far as germanium sesquioxide, FDA said in an import alert from 2011 that germanium “is a nonessential trace element that has caused nephrotoxicity (kidney injury) and death when used chronically by humans, even at recommended levels of use.”
And in 2008, FDA also sent a letter of non-objection to Bergstrom Nutrition recognizing MSM as GRAS as a food ingredient. The nominators of all of these substances will be invited to make a short presentation supporting the nominations.
In addition to the FDA meeting, USP recently released for comment the proposed revisions to General Chapter <797> Pharmaceutical compounding – Sterile Preparations.
Major revisions of the general chapter include: A reorganization of existing sections and procedural information; Condensing the three compounded sterile preparation (CSP) microbial risk categories (e.g. low-, medium-, and high-risk) into two categories (Category 1 and 2) distinguished primarily by the conditions under which they are made and the time within which they are used; removal of information on handling hazardous drugs and added cross-references to <800> Hazardous Drugs—Handling in Healthcare Settings; and an introduction of the terminology “in-use time” to refer to the time before which a conventionally manufactured product used to make a CSP must be used after it has been opened or punctured, or a CSP must be used after it has been opened or punctured.