Asia-Pacific Roundup: TGA allows pharmacy-level subs to counter amoxicillin shortage

Australia’s Therapeutic Goods Administration (TGA) is allowing pharmacists to dispense amoxicillin in different dosage forms that those stated on the prescription to mitigate shortages of liquid, tablet and capsule formulations of the antibiotic.
 
In a Serious Scarcity Substitution Instrument (SSSI), TGA declared most oral amoxicillin products as “scarce” medicines and cleared pharmacists to substitute certain formulations without getting prior approval of the prescriber.
 
Specifically, TGA declared four amoxicillin suspension dosages to be scarce and empowered pharmacists to use whichever dose they have available to fulfill prescriptions for any liquid preparation of the antibiotic. Pharmacists also can provide any of the four amoxicillin suspensions when asked to dispense the antibiotic as a powder for oral liquid.
 
Similarly, the SSSI allows pharmacists to dispense oral 250mg, 500mg and 1g doses of amoxicillin when a prescription requests tablets or capsules that are scarce. The agency declared 500mg capsules and 1g tablets to be scarce. TGA did not declare 250mg capsules as scarce medicines “because of the potential impact this would have on supply of the liquid formulations.”
 
The SSSI took effect last week and is scheduled to stay in force until 31 May 2023. TGA can revoke the instrument before the expiry date if the serious scarcity is resolved, or safety concerns are identified.
 
TGA said the shortages “are due to manufacturing issues at a major supplier leading to unexpected increases in demand for alternative suppliers.” Other countries also face supply constraints. In the US, the Food and Drug Administration and the American Society of Health-System Pharmacists have issued notices about the shortage.
 
According to FDA, some Sandoz product lines are unavailable, and others have limited availability. Limited supplies of the unavailable products are due to arrive by the first quarter of 2023. With Sandoz off the market for now, Aurobindo, Hikma Pharmaceuticals and Teva Pharmaceuticals are seeing increased demand for their products. Amoxicillin products from the three companies are either only available in the US to existing customers or subject to limit distribution.
 
TGA Notice
 
India’s NPPA makes more changes to pharmaceutical database in response to feedback
 
India’s National Pharmaceutical Pricing Authority (NPPA) has made further changes to the Integrated Public Database Management System 2.0 (IPDMS) as it continues to refine the service in response to feedback from stakeholders.
 
Last month, NPPA published details of 40 pieces of feedback and its responses to the comments. The latest NPPA memo brings information on the drug price watchdog’s response to the earlier feedback up to date and adds details of another 16 suggestions that it has received and acted on since publishing the original overview.
 
The new feedback covers requests to fix bugs, such as the “state details being shown wrongly for plant details,” and to make revisions including changing the date format and allowing users to update brand names. NPPA has already implemented many of the suggestions, for example by allowing users to change product details, other than switches from scheduled to non-scheduled, without its approval.  
 
NPPA has also completed some of the work that it initiated in response to the earlier feedback, such as the removal of a plant verification process that was taking up to three weeks. Other work, including an analysis of the impact of adding a drop-down menu of the strength of active pharmaceutical ingredients, is still ongoing.
 
NPPA Memo
 
Indonesia's BPOM revokes manufacturing certificate after finding contaminated syrups
 
The Indonesian Food and Drug Authority (BPOM) has revoked PT Rama Emerald Multi Sukses’ (PT REMS) good manufacturing practice (GMP) certificate for non-beta-lactam oral liquids after the discovery of contaminated syrups led it to inspect facilities.
 
BPOM is continuing to look for contaminated syrups in the wake of manufacturing and supply chain problems that are implicated in the deaths of 195 children. BPOM found syrups from PT REMS that contained ethylene glycol and diethylene glycol levels of 33.46% and 5.94%, respectively. The threshold for contamination is 0.1%.
 
The authority subsequently inspected the company’s production facilities and found GMP discrepancies. The inspection led BPOM to revoke the GMP certificate and distribution permits for all 32 medicinal syrups made by the company.
 
In addition to the administrative sanctions, the authority ordered PT REMS to stop production of all medicinal syrups, withdraw existing syrups from the market, destroy its stocks in the presence of BPOM officials and report on the implementation of the orders. Further investigations will follow if BPOM finds preliminary evidence that a crime has been committed.
 
BPOM Notice (Indonesian)
 
TGA investigates potential nitrosamine contamination of ACE inhibitor
 
TGA is investigating potential contamination of quinapril medicines with very low levels of a nitrosamine impurity. Sponsors of all marketed drugs containing the angiotensin converting enzyme (ACE) inhibitor have paused supply while TGA looks into the presence of the contaminant N-nitroso-quinapril.
 
Five companies including Pfizer sell a range of formulations containing quinapril, as a single agent and in combination with the diuretic hydrochlorothiazide, in Australia for the treatment of high blood pressure. TGA has learned that “very low levels” of N-nitroso-quinapril have been detected in all quinapril products supplied in Australia, including those that contain hydrochlorothiazide.
 
While the contaminated medicines pose no immediate health risk, the sponsors of all quinapril products sold in Australia have paused supply. All quinapril batches known to contain unacceptable levels of the nitrosamine have been recalled from pharmacies.
 
Multiple quinapril products, including five sold by Pfizer, are listed as unavailable in TGA’s drug shortage database. Pfizer lists 30 April as the expected supply date for its products, while two other pharma companies, Apotex and Generic Health, have given dates in January. TGA has told patients to talk to their doctors about alternative treatments they can take while quinapril products are off the market.
 
TGA Notice
 
Japanese Pharmacopoeia seeks feedback on draft lithium carbonate tablet monograph
 
The Japanese Pharmacopoeia has released a draft monograph on lithium carbonate tablets for public consultation and will accept feedback until the end of February.
 
In the draft, the Japanese authority states that lithium carbonate tablets must contain between 95% and 105% of the labeled amount of the active pharmaceutical; the same range used in the US.
 
The rest of the Japanese monograph covers the uniformity of dosage units, dissolution testing and other assessments of the tablets. The Japanese Pharmacopoeia is asking interested parties to identify parts of the text they want to change or comment on and provide their reasons for proposed revisions.
 
PMDA Notice
 
Other news:
 
Singapore’s Health Sciences Authority (HSA) has published a notice about the recall of non-absorbable sutures sold by Medtronic. The recall follows the discovery of a potential sterile barrier breach linked to manufacturing errors in the packaging that may cause a gap or wrinkle in the breather pouch seal. A breach could lead to infection or vision loss for ophthalmic procedures. HSA Notice