Asia-Pacific Roundup: TGA guidance details management of GMP compliance signals

Australia’s Therapeutic Goods Administration (TGA) has published guidance on the management of good manufacturing practice (GMP) compliance signals for domestic and overseas manufacturers of medicines and biologicals.
 
Compliance signals include “intelligence, data and information” that TGA receives that indicate a manufacturer has departed from GMPs. The signals come from “various internal and external intelligence sources, as well as our inspections and routine compliance monitoring process,” the agency said. Sponsors and manufacturers are expected to report known or potential signals.
 
The guidance describes how TGA manages the signals it receives and its response. TGA triages signals with consideration of an expanded set of factors for overseas sites that includes the impact to supply in Australia, then reviews and investigates to determine if it needs to take compliance action.
 
TGA may ask sponsors to provide risk assessments to support the continued use of products from facilities with GMP compliance signals. The agency also may request materials such as inspection reports and evidence of corrective and preventive actions.
 
TGA uses the information to rate a facility on a four-point scale of compliance risk that ranges from low to critical. Manufacturers are classified as low risk if they are committed to doing the right thing, have effective quality management systems and are run by compliance-oriented managers. In that scenario, TGA will “make on-going compliance easy through clear education.”
 
The agency reserves the critical category for manufacturers that choose to be noncompliant and have a “reckless attitude to manufacturing licence obligations.” Faced with such a manufacturer, TGA may pursue penalties including criminal offences and infringement notices. TGA has a larger set of potential regulatory actions when dealing with domestic manufacturers.
 
TGA Guidance
 

PMDA sets out plan for accelerating medical devices access

Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has published details on how it plans to accelerate the approval process for advanced medical devices that address unmet medical needs.
 
PMDA has already shortened medical device review times. In fiscal 2019, PMDA typically took 11.1 months to review normal devices and 7.3 months for priority candidates, beating its respective targets of 14 months and 10 months. PMDA chief executive Fujiwara Yasuhiro said the data show “the device lag that had previously been a problem in Japan” is now a thing of the past.
 
PMDA now is trying to accelerate access to specific groups of products. Yasuhiro highlighted four specific initiatives.
 
A breakthrough device program, called Sakigake, provides priority access to PMDA, enhanced pre-submission consultation, and accelerated review to devices that impress in early-phase clinical trials. PMDA has set a six-month target review timeframe for Sakigake devices.
 
Yasuhiro also highlighted as other examples of how PMDA is supporting development regulatory privileges for devices designed for use in children and a conditional early approval system. The conditional approval system is intended to enable access to devices that address significant unmet needs but are hard to study in conventional confirmatory clinical trials.
 
Finally, PMDA’s IDATEN initiative caters to the emergence of medical devices that continue to change after coming to market, such as products based on artificial intelligence. When reviewing such devices, PMDA will confirm change plans so that the authorization holder can quickly make certain partial amendments to their approvals.
 
PMDA Statement
 

PMDA shares guidance on the use of registry data in applications

PMDA has published English-language versions of two recent documents on the use of registry data in applications involving drugs, medical devices and regenerative medical products in Japan.
 
One document sets out basic principles for the use of registry data, discussing five scenarios in which companies may use registry data, for example to act as a control in single-arm clinical trials and to support post-market evaluations of safety and efficacy.
 
Another section of the text provides general points to consider for all the applications of registry data, including the need for researchers to protect the personal information of patients in the registry and consider the reliability of the data.
 
The second document focuses on the reliability of registry data. In that text, PMDA explains concepts for ensuring the reliability of registry data and compliance matters for applications using the information. The compliance matters include the need to confirm the data quality management implemented by the registry holders and to follow a predetermined statistical analysis plan.
 
PMDA sees barriers to the use of registry data today, such as the fact most real-world data is not optimized for use in the evaluation of safety and efficacy, but also sees opportunities to address the issues. The agency expects use of registry data to increase as the industry gains more experience and medical information communication technologies advance.
 
PMDA Guidance, More
 

Gilead withdraws filgotinib filing after TGA raises toxicity concerns

Gilead Sciences has withdrawn its application for approval of filgotinib in rheumatoid arthritis in Australia. The company pulled the filing after TGA followed the US FDA’s concerns about the safety of the JAK1 inhibitor.
 
The US FDA issued a complete response letter to Gilead last year because of concerns about the effect of filgotinib on sperm parameters and broader concerns about the benefit-risk profile of the 200 mg dose. TGA’s Advisory Committee on Medicines flagged up similar issues during its review of the drug, leading it to conclude it “had an overall negative benefit risk profile for the proposed indication.”
 
Gilead withdrew its filing before TGA reached a decision on whether to approve filgotinib, which is sold as Jyseleca in the EU. Trials designed to assess the reproductive toxicity of the drug — the primary concern of the TGA committee — began in 2017 and 2019.
 
Assessment Report
 

India drops convalescent plasma from COVID treatment guidance

India has removed convalescent plasma from its guidelines for treating COVID-19. Guidance previously said physicians could consider the off-label use of convalescent plasma for patients with early, moderate disease.
 
In updating its advice, a joint task force of members of the All-India Institute of Medical Science and Indian Council of Medical Research removed convalescent plasma from the short list of emergency authorized and off-label treatments that may be used in specific circumstances. The list now only features the antiviral remdesivir and anti-IL-6 monoclonal antibody tocilizumab.
 
India’s Central Drugs Standard Control Organization (CDSCO), which has never cleared convalescent plasma for on-label use in COVID-19, shared news of the change in the treatment guidelines without comment.
 
AIIMS Guidance, CDSCO Notice
 

Other news

TGA has updated its guidance on the process for getting medical devices included in the Australian Register of Therapeutic Goods with revised requirements for sponsors. TGA Guidance