Asia-Pacific Roundup: CDSCO advises drugmakers to only use pharma-grade excipients from approved sources

India’s Central Drugs Standard Control Organization (CDSCO) has published advice intended to prevent the contamination of cough syrups with ethylene glycol (EG) and diethylene glycol (DEG).

As CDSCO explained, “it is of paramount importance” that drug formulations are made in compliance with the prescribed standards, “not only in respect of API but also various excipients.” The hundreds of deaths linked to EG and DEG contamination have shown the importance of excipient sourcing and, with India now in one of its cold and flu seasons, use of cough syrup could rise in the coming months.

“Manufacturers are hereby advised that they should purchase and use only pharma grade excipients from their approved sources/vendors which are of quality standards in accordance with the regulatory requirements,” CDSCO wrote. The sourcing recommendations are intended to ensure the quality, safety and efficacy of drugs made and sold in India.

CDSCO posted its notice days before the World Health Organization (WHO) shared another alert about contaminated syrup and suspension medicines. The WHO alert refers to five products initially detected in the Maldives and Pakistan and reported to the public health body last month. Since then, Belize, Fiji and Lao People’s Democratic Republic have found some of the affected products.

In the notice, WHO describes the actions taken to date, explaining that work by the Maldives Food and Drug Authority and Australia’s Therapeutic Goods Administration (TGA) showed five batches of a syrup were contaminated with EG. Officials in Pakistan then inspected Pharmix Laboratories, the stated manufacturer of the products, and found EG and DEG may be present as contaminants in other products and batches made by the company.

WHO’s alert specifically relates to five products. However, the organization is recommending “increased vigilance and testing in respect of oral liquid dosage medicines” made by Pharmix between December 2021 and December 2022 “out of an abundance of caution.”

CDSCO Notice, WHO Notice

TGA seeks feedback on new draft quality standards for MDMA and psilocybin

Australia’s TGA has released draft quality standards on MDMA and psilocybin for consultation as it works to ensure the consistent production of the recently rescheduled molecules.

In July, Australia rescheduled MDMA and psilocybin, respectively the active ingredients in the illicit drug ecstasy and psychedelic magic mushrooms. The change permitted the use of the molecules as controlled drugs in trials targeting post-traumatic stress disorder, for MDMA, and treatment resistant depression, for psilocybin.

Under the new rules, TGA expects broader access to MDMA and psilocybin to bring “greater quantities into supply” and necessitate the introduction of the first quality standards for the molecules. TGA wants to introduce standards in the belief “minimizing variation between batches of products, and mandating adherence to agreed quality requirements, is essential to support the known safety and efficacy.”

The agency has developed the standards in consultation with domestic and international manufacturers that supply MDMA and psilocybin for clinical trials. The talks informed the proposed requirements and testing methodologies that TGA released for consultation last week.

TGA provided draft quality standards for MDMA and psilocybin in separate annexes to the consultation. The consultation itself features five questions about each draft standard. Two of the questions address whether people agree with the proposed tests and limits for impurities, residual solvents and heavy metals. TGA said it is not seeking comment on the decision to publish new quality standards for MDMA and psilocybin.

Another question is focused on a proposed requirement for unlicensed compounding pharmacists to use an active pharmaceutical ingredient that has been tested in an Australian good manufacturing practice (GMP)-licensed laboratory. The agency wants to know if people agree with its plan to require ingredients to undergo testing at a GMP-licensed laboratory before being used in extemporaneous compounding.

TGA is accepting feedback until the end of January. The agency expects to finalize the quality standards in February and include them in the Federal Register of Legislation the following month. While TGA plans to implement the requirements as soon as the orders commence, it expects minimal disruption because the proposals are consistent with requirements currently applied to medicines used in clinical trials. One of the five questions asks whether the respondent agrees with the targeted March implementation date.

Consultation Paper

TGA extends transition to nitrosamine restriction to avoid shortages of diabetes medicines

TGA is allowing manufacturers to continue supplying sitagliptin medicines contaminated with levels of a nitrosamine impurity above the acceptable intake (AI) limit for longer than originally planned. The change in the enforcement timeline is intended to prevent a shortage of the diabetes medicines.

Last year, TGA investigated the contamination of sitagliptin, the active ingredient in Merck & Co.’s Januvia, with the nitrosamine impurity NTTP. The investigation led TGA to set the acceptable limit of the impurity at 37 ng per day. TGA assessed the risk of an intake level of up to 246 ng per day until 31 May 2023 and determined short-term exposure poses a minimal additional cancer risk.

Seeking to avoid a shortage, TGA deferred the enforcement of the 37 ng limit. Last week, the agency published a follow-up notice, in which it described a further investigation that found no increased health concerns from an intake level of NTTP of up to 246 ng per day until 30 June 2024.

“Consistent with international regulatory approaches, including in Europe and the United States, we are temporarily allowing sponsors to supply sitagliptin products with trace amounts of NTTP above the AI level to the Australian market to ensure that patients have continued access to this essential medicine,” TGA wrote.

The agency expects sponsors to monitor and report NTTP levels “while they address the presence of the impurity.” TGA is also working with sponsors to “oversee the implementation of improved manufacturing and testing processes.”

TGA Notice

Japan’s PMDA warns of scam phishing emails pretending to come from its staff

Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has warned companies that scammers are posing as its staff in phishing emails.

PMDA has confirmed that people are sending emails pretending to be agency employees to try to gather information from the recipients. The agency has provided an example of a phishing email, which has the title “PMDA Office of Manufacturing Quality” and comes from an address featuring the name of a non-existent PMDA employee. The email address domain is similar to PMDA’s domain.

The agency is asking anyone who receives a suspicious email to contact the relevant office or submit information using its English-language form. PMDA has warned the recipients of suspicious emails not to open any files attached to the message or reply.

The notice comes three years after PMDA warned that scammers had created fake versions of its website to steal information or money from visitors. Other regulators, including the European Medicines Agency, have also warned about phishing emails in the past.

PMDA Notice

Other News:

The Drug Regulatory Authority of Pakistan (DRAP) has ordered the recall of a substandard batch of sterile water for injection because of an endotoxin risk. A government laboratory ruled the batch of the water, which is mainly used as a solvent or diluent for parenteral drugs, is substandard. Endotoxins can threaten life when injected intravenously. DRAP Notice

Asia-Pacific Roundup: CDSCO advises drugmakers to only use pharma-grade excipients from approved sources

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