Asia-Pacific Roundup: Pakistan’s DRAP issues warning after manufacturers fail to mitigate glycol impurity risk

The Drug Regulatory Authority of Pakistan (DRAP) has warned medicine manufacturers for neglecting “to verify the quality and safety of their raw materials from authorized vendors” to prevent diethylene glycol (DEG) and ethylene glycol (EG) impurities.

Over the past few months, DRAP has found raw materials and finished products that contain DEG and EG, contaminants linked to a series of recalls and more than 100 deaths globally in recent years. Late last year, the agency ordered the recall of five syrups and suspensions in response to suspicions that a single batch of Alergo syrup was contaminated with DEG and EG. In January, DRAP found EG in a batch of the excipient propylene glycol.

After finding the potentially deadly impurity in the batch, DRAP told drug manufacturers to screen raw materials for EG and DEG before using them in oral liquid preparations. However, the regulatory agency is concerned that the industry is failing to act on its instructions.

In the latest warning, DRAP said “many therapeutic goods manufacturers” are neglecting to verify their raw materials “despite repeated warnings and instructions.” Pakistan’s Central Drug Laboratory, Karachi, is analyzing raw materials and finished products for EG and DEG contamination. DRAP wants manufacturers to test their raw materials to prevent a “potential influx of contaminated products in the market.”

“In view of the criticality of the matter and potential for untold human tragedy, the therapeutic goods industry is once again warned to screen raw materials (propylene glycol, glycerin, and sorbitol) for contamination with EG and DEG before using these materials in the manufacturing of oral liquid preparations. Additionally, all finished products must be analyzed for EG and DEG contamination before their release into the market,” the agency wrote.

DRAP listed specific actions it wants the pharma industry to take. Manufacturers should implement supplier qualification programs, verify the traceability and authenticity of the raw material using unique identifiers such as barcodes or RFID tags, conduct regular risk assessments, and monitor the performance of their suppliers. DRAP also wants companies to educate and train staff and suppliers on preventing contamination and checking for signs of poor printing, misspellings, and inconsistent logos.

The focus reflects DRAP’s belief, based on investigations into earlier contaminations, “that the main problem lies with the integrity of [the] supply chain of raw material which appears to be compromised.”

DRAP Notice

India’s NPPA threatens penal action over ‘blatant and deliberate’ breaches of pricing law

India’s National Pharmaceutical Pricing Authority (NPPA) has warned companies that launch new drugs before having their prices fixed and notified may face penal action.

In a notice to the pharma industry, NPPA said some companies are launching medicines immediately after filing a Form-I price fixation application. NPPA called decisions to start selling drugs, including new combinations, strengths, and dosages, without waiting for the retail price to be fixed and notified a “blatant and deliberate violation” of the rules.

“All the pharmaceutical manufacturers are, hereby, advised to refrain from such practice and to ensure strict compliance with the extant provisions of law. Otherwise, NPPA would be constrained to initiate penal action against the defaulting manufacturers,” the drug price watchdog wrote.

NPPA cited the Drugs Prices Control Order, 2013 as a source of its power to take penal action. The order empowers Indian authorities to charge manufacturers a penalty, plus the amount they overcharge above the fixed and notified price, if they fail to apply for prior approval of the price of the new drug using Form-I.

NPPA Memo

TGA updates nitrosamine impurity acceptable intakes in response to European actions

Australia’s Therapeutic Goods Administration (TGA) has updated its information on the acceptable intake (AIs) of nitrosamine impurities in response to revisions to the position of European authorities.

Last month, the European Medicines Agency (EMA) revised a question-and-answer document about the AIs of nitrosamine impurities. The changes included adding new impurities for products such as the schizophrenia drug aripiprazole, which is sold under the brand names Abilify and Aristada, to an annex that lists the types of nitrosamines associated with various active ingredients.

TGA updated its position in response to the EMA's action. “The changes include minor editorial amendments, increases to the AI limit for a nitrosamine impurity, and inclusion of recently internationally determined AI limits for numerous nitrosamine impurities in medicines,” the Australian agency wrote.

Officials expect sponsors and manufacturers to be familiar with the current AIs for nitrosamine impurities. The updated TGA list of nitrosamine impurities features 36 entries added or updated on 31 January.

TGA Notice

Philippine FDA posts warning about increased risk of corticosteroid misuse and abuse

The Philippine Food and Drug Administration (FDA) has published safety information about topical corticosteroids in response to the increased risk of misuse and abuse.

Topical corticosteroids treat skin disorders such as eczema, dermatitis, and psoriasis and are typically administered once or twice a day. FDA is concerned that the products are being misused.

“Misuse, abuse and abrupt stop of topical corticosteroids result in topical steroids withdrawal (‘topical steroid addiction’ or ‘red skin syndrome’). This includes prolonged, frequent and inappropriate use of moderate to high potency topical corticosteroids, especially on the face and genital area,” FDA wrote. Excessive use of the drugs can cause redness of the skin and a burning sensation, followed by skin peeling.

To mitigate the risk, FDA has advised healthcare professionals and the public. The agency is advising healthcare professionals to tell their patients about the risk of topical steroid withdrawal and instruct them on how to use the products safely. FDA is asking the public not to share prescription medicines with friends or relatives or self-diagnose and treat skin conditions.

FDA Notice

Singapore’s HSA shares alert about cracked cartridges used with Novo Nordisk insulin

Singapore’s Health Sciences Authority (HSA) has shared a warning about cracks in some cartridges used with Novo Nordisk insulin products.

The company wrote to healthcare professionals after discovering “3 ml cartridges with circular non-penetrating cracks on the outer surface of the cartridge around 4-6 mm below the ‘shoulder’ of the cartridge,” HSA wrote. The defect affects one cartridge per 4,444 boxes. HSA advises healthcare professionals to inspect cartridges before dispensing them, when possible.

The agency published the notice days after Australian authorities passed on an urgent product defect alert from Novo Nordisk that described the same type of crack. In that alert, the company advised customers that “there is no risk of evaporation or contamination” because “the integrity of the cartridge remains intact.”

If a cartridge cracks while being handled, it will leak and “be detectable by the patient.” The cracked cartridge will not work in the drug delivery pen. Novo Nordisk told customers that it has identified and resolved the “manufacturing root cause that created this issue.”

HSA Notice

Other news:

DRAP has approved International Atomic Energy Agency technical reports on radiopharmaceutical production and quality control as references for regulating the products in Pakistan. DRAP Notice

TGA has shared details of a problem with the dose counter on some batches of Boehringer Ingelheim’s Spiriva Respimat, an inhaled treatment for chronic obstructive pulmonary disease and asthma. TGA Notice

Asia-Pacific Roundup: Pakistan’s DRAP issues warning after manufacturers fail to mitigate glycol impurity risk

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