Australian Pharma Under Pressure To Provide Full Documentation For GMP Clearance
Executive Summary
Pharma firms in Australia have been told to up their game when applying for GMP clearance of overseas manufacturing plants. The Therapeutic Goods Administration says too many applications don’t contain all the necessary documentation, and from Sept. 26 new processes will be introduced putting more of the onus on sponsors.
The Australian regulator, the Therapeutic Goods Administration, appears to have lost patience with companies that fail to provide the correct documentation when seeking good manufacturing practice (GMP) clearance for overseas manufacturing plants, and from Sept. 26 it is introducing a new process that will put pressure on applicants to get their submissions right first time.
With clearance applications continuing to rise, the new process is expected to cut down on the legwork the TGA has to do to ensure companies include all the relevant documentation with their submissions. The agency is also planning to publish revised guidance and a new electronic tool to make it easier for applicants to determine exactly what evidence they need to provide.
Under the current guidance, which dates from May 2011, sponsors wishing to market drugs manufactured outside Australia must file an application for GMP clearance and ensure they include all the required documentation, otherwise the clearance may not be issued.
Clearance can be granted in one of three ways: after a TGA on-site inspection, under a mutual recognition agreement with the source country, or through “compliance verification” – i.e., on the basis of a recent GMP inspection report by an overseas regulator.
The number of applications for GMP clearance has risen sharply in recent years, from about 4,000 in 2014/15 to more than 6,000 in 2016/17, and the figure is expected to continue to rise, the TGA says. However, more than 60% of applications under compliance verification (CV) “do not provide all required supporting evidence to demonstrate that the manufacturing site is acceptable for the supply of therapeutic goods to the Australian market.”
The agency issued an initial warning about this in January this year, when it said that the documents most commonly missing from applications included the GMP agreement between the sponsor and the manufacturer, a copy of the most recent inspection report, the latest product quality review, a list of regulatory inspections and any regulatory actions in the past three years – such as product alerts, warning letters, and recalls due to defects – and the manufacturer’s declaration for active pharmaceutical ingredients (APIs).
In such cases, the TGA has to contact the applicants and ask for the missing evidence, and “often this process involves several attempts on our behalf for each application before appropriate evidence is received.”
“Process Improvements”
The agency says it is therefore implementing some “process improvements” to ensure that applicants that do provide all the required information are not disadvantaged and at the same time reduce its processing times.
“Irrespective of whether the requested information has been received, we will progress the application to assessment” – TGA
For CV applications submitted before Sept. 26, 2017, the TGA will provide applicants with one opportunity to submit any outstanding supporting evidence during the application receipt stage – i.e., before the application is moved to the assessment stage. The agency will specify a due date, after which, “irrespective of whether the requested information has been received, we will progress the application to assessment.”
For CV applications submitted on or after Sept. 26, once payment of all outstanding fees has been received, the application will move to the assessment stage. “We will not conduct an assessment of the information you submit in support of your application during the application receipt stage,” the agency says.
During the assessment, the TGA will make a determination on the application, “taking into account the information and evidence provided with the application.” If any deficiencies are identified or clarification is needed, the applicant will be given a written confirmation of the deficiencies, and a date by which a response is due.
“After this due date, we will make a determination on your application, regardless whether we have received a response from you. The determination will be made based on the information available. It is therefore important that you familiarise yourself with the information requirements specified in the GMP clearance guidance.”
To help applicants prepare their applications, the TGA says it will shortly be publishing revised guidance on GMP clearance as well as introducing a new web-based GMP Clearance Application Assistance Tool (CAAT) and re-designed application forms.
“Prior to submitting your GMP clearance application we strongly encourage you to refer to the GMP clearance guidance and CAAT to determine the evidence required to support your application,” it adds.
Get The Scope Right
The agency also warns companies to make sure that the scope of their application “accurately reflects the dosage forms and/or manufacturing steps performed by the overseas manufacturer.”
From Sept. 26, clearances will be issued for “the scope that is supported by the evidence provided and you may not be contacted prior to finalising the application,” it says.
It gives some examples of how it might manage incorrect application scopes:
- Finished product dosage forms – if the dosage form described in the application is a group term containing several other dosage forms that are not supported by the supplied evidence, the scope will be changed to the dosage forms specifically supported by the evidence.
- Finished product steps of manufacture – if the manufacturing step is a group term that contains several manufacturing steps that are not supported by the evidence, the scope will be changed to the manufacturing steps that are specifically supported by the evidence.
- API applications – if the manufacturing step described is “active material manufacture”, but the evidence shows that the site does not perform microbiological testing, the manufacturing step will be changed to “active material manufacture excluding microbiological testing.”
- If the sponsor includes what the TGA describes as a “nonsensical scope” in the application – for example, “non-sterile injection dosage forms” – the TGA will change this accordingly, for example to “sterile injection dosage forms.”
From the editors of Scrip Regulatory Affairs.