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Australian manufacturing licences and GMP for medicines and biologicals

11 August 2021

Duration: 
18 minutes 19

Join us for this episode as we speak with Nadia Saleh, Inspector in the Manufacturing Quality Branch at TGA and discuss:

  • what role TGA plays in ensuring quality manufacturing practices and why this is important
  • what Good Manufacturing Practice (GMP) is
  • how this applies to manufacturers of medicines and biologicals
  • the inspection process
  • how COVID-19 has affected the way we work

Host: Steven Smith-Fleury

Guest: Nadia Saleh


Welcome to the Therapeutic Goods Administration's podcast series, SME Assist - Navigating therapeutic goods regulation. We appreciate that the regulation of therapeutic goods can be challenging to understand. Throughout this series, we aim to help small to medium enterprises, researchers, start-ups and anyone new or unfamiliar with regulation to understand their obligations when it comes to supplying therapeutic goods in Australia.

Please note that the information provided to you throughout these podcasts is without prejudice. It is not binding on the TGA, and you should get your own independent legal advice to ensure that all of the legislative requirements are met.

Steven Smith-Fleury

Hi, I'm Steve, from the SME Assist Team at the TGA. Welcome to the fourth episode in our series of podcasts about navigating therapeutic goods regulation in Australia. If you haven't already, please be sure to hit subscribe, and listen to our previous episode where we discuss the TGA Laboratories.

Today we’re going to be talking with Nadia Saleh about Australian manufacturing licenses, good manufacturing practice and how COVID-19 has changed the way inspections are carried out. Today we are only covering medicines and biologicals, not medical devices.

Nadia is part of a team that’s responsible for inspecting manufacturing facilities that process human blood, tissues and cellular products. Welcome, Nadia, and thanks for joining us today.

Nadia Saleh

Thanks for having me, Steve.

Steven Smith-Fleury

So, Nadia, firstly, can you tell us a bit about manufacturing of medicines and biologicals, and our role in this process?

Nadia Saleh

Sure. The Therapeutic Goods Act, with certain exceptions, requires that the Australian manufacturers obtain and maintain a good manufacturing practice or GMP license, and that overseas manufacturers obtain and maintain a GMP certificate issued by the TGA. Those goods also need to be registered and included in the Australian Register for Therapeutic Goods or ARTG.

Manufacturing therapeutic goods for human use without a GMP license or certificate, except for those exempted from the TGA regulatory requirements, is an offence that carries heavy penalties.

Steven Smith-Fleury

So, what does, having a GMP license or certificate actually mean for the manufacturer, Nadia?

Nadia Saleh

TGA issues a GMP license or certificate to manufacturing, sites when they demonstrate compliance with the GMP standard relevant to the therapeutic good.

Steven Smith-Fleury

And how would they go about gaining one?

Nadia Saleh

To obtain a GMP license or a certificate for a new manufacturing site, the manufacturer needs to submit an application to the TGA. The application is reviewed by the Manufacturing Quality Branch and assigned the inspection team to conduct an onsite inspection of the manufacturing site to assess its suitability. During the inspection the inspectors will also assess suitability of site equipment, personnel, quality system, documentation of activities and computer systems used.

When the inspection is completed and any issues raised during the inspection are satisfactorily addressed by the manufacturer, the inspection will be closed. The TGA will then issue the manufacturer with GMP license or certificate. To maintain licensing or certification of a manufacturing site, TGA also conducts periodic inspections to asses ongoing compliance with GMP standards. Ongoing site inspections are scheduled by the TGA applying a risk-based approach.

Steven Smith-Fleury

So, just for our listeners who might not be familiar with it, what is good manufacturing practice, Nadia?

Nadia Saleh

The term good manufacturing practice is used to describe a set of principles and procedures which when followed by manufacturers of medicines and biologicals helps ensure that the products manufactured will have the required quality.

Steven Smith-Fleury

Thanks Nadia, I’m sure this provides a level of confidence that the product is safe for use.

Now, you mentioned that we use a risk-based approach in relation to manufacturing. Can you tell us a bit more about that?

Nadia Saleh

Sure. TGA applies a risk-based approach to determine the frequency of ongoing inspections, as well as the emphasis and depth of inspections. This approach is guided by the inherent risks of the product, method of manufacture and the previous inspection compliance rate of the site.

We use inspection frequency matrices to guide the frequency of inspections.

Steven Smith-Fleury

So, that might not be a term that our listeners have heard before, Nadia. What is a frequency matrix?

Nadia Saleh

The frequency of periodic inspections for manufacturing sites of different goods will increase or will be increased or reduced depending on use of the on the use of the good and associated manufacturing processes. For example, the period between inspections for prescription medicine is shorter than that assigned for a complementary medicine manufacturing site.

Steven Smith-Fleury

Can you tell us a bit more about what goes into planning an inspection?

Nadia Saleh

In planning our inspection programme, we consider information including emerging product trends, such as recalls and adverse event reports, results of TGA Laboratory testing of the manufactured goods, feedback received from inspections undertaken by other regulators, the manufacturer compliance history, and any significant changes within the company, including introduction of additional product or products, and changes to manufacturing process.

Steven Smith-Fleury

Thanks, Nadia. It sounds like there's quite a lot that goes into planning these inspections. Now, we do understand that manufacturers are usually notified of an upcoming inspection. Can you give us an example of when this might not happen?

Nadia Saleh

Where necessary, an unannounced inspection may be undertaken at any time outside of the regular inspection cycle, or the date or the next scheduled inspection may be brought forward. We might conduct an unannounced inspection where it is believed that the true extent of compliance cannot be assessed through a routine inspection that the manufacturer can prepare for.

Steven Smith-Fleury

Now, are you able to tell us a bit about what's involved in the GMP inspection process, and how it works?

Nadia Saleh

Generally, the inspection process starts when the scheduling of the inspection of a manufacturing site and allocation of an inspection team. The inspection process involves three phases. Pre-inspection activities, the inspection and post-inspection activities. The pre-inspection activities include advising the manufacturer of the expected inspection dates and the number of the TGA inspection team members. The inspection team will also request pre-inspection information for review in advance of the inspection.

On the first day of the inspection, the inspection team will hold an opening meeting with the manufacturer's management and key personnel to explain the inspection process and plan. During the inspection, the inspection team will observe some manufacturing activities, review the manufacturer quality system documentation and request additional evidence as required. Samples may be taken for laboratory testing by the TGA, especially for medicines manufacturing sites.

At the end of the inspection, the inspection team will, will hold a closing meeting to provide an overview of the inspection and its outcome, provide the manufacturer with a list of deficiencies, and discuss their resolution.

Steven Smith-Fleury

Thanks, Nadia. Now, can you just briefly explain to us what happens after an inspection?

Nadia Saleh

After the inspection, the manufacturer is provided with written results of the inspection highlighting deficiencies observed by the TGA. Deficiencies are classified as critical, major or other, depending on the risks associated with each deficiency

Steven Smith-Fleury

Nadia, just around deficiencies. Can you give us an example of what a deficiency might be?

Nadia Saleh

Deficiency might be a diversion from, documented procedures or regulatory requirements. Diversion from regulatory requirements might be classified as a major.

Diversion from processes could be major or minor, depending on the nature of the diversion.

Steven Smith-Fleury

Okay. Thank you.

Nadia Saleh

The manufacturer is allowed up to three rounds of responses to address all deficiencies. Once all deficiencies have been addressed, the inspection team will provide an inspection closeout letter with the final outcome of the inspection.

Steven Smith-Fleury

Thanks, Nadia. Now, can you tell us a bit about the remote inspection programme? I understand that’s been implemented in response to COVID-19.

Nadia Saleh

Correct. COVID-19 obviously had a major impact on our ability to safely conduct inspections. So, like the rest of the working world, we had to quickly adapt to working in a remote environment. Our remote inspection process was designed to manage the impact of COVID-19 on the conduct of inspections including the travel restrictions and social distancing requirements.

Remote inspections allowed the TGA to continue to monitor unlicensed manufacturers of therapeutic goods. TGA has been conducting remote inspections of Australian and overseas manufacturing sites since May 2020.

Steven Smith-Fleury

That’s great. So, how are they actually carried out, Nadia?

Nadia Saleh

With the implementation of the remote inspection programme, the principles of the inspections remain the same. However, they are undertaken remotely through the use of technology, not requiring inspectors to physically attend manufacturing sites. Some changes to our routine inspection process include inspectors will contact, manufactures to announce the inspection, explain the remote inspection process and agree on the suitable telecommunications software for use during the inspection.

Remote inspections involve virtual interviews with the manufacturers' key personnel, facility tours, observation of processes and activities and remote desktop assessment of the manufacturer quality system documentation.

Inspectors have utilised different software and technologies to conduct the inspections such as MS Teams and Webex. Otherwise, the inspection process is unchanged and we've been able to conduct thorough inspections in essentially the same way.

Steven Smith-Fleury

So, Nadia, you’ve mentioned some of the technologies and software that’s been used to conduct inspections. Have we used anything like drones or anything like that to do walkthroughs of manufacturing sites?

Nadia Saleh

We are restricted by what the department allow us to use, of available software and we are restricted by what the Department of Health allow us to use. But sometimes we also use, WhatsApp, FaceTime, we used Viber, FaceTime, just to assist the manufacturer with the tour. If they are going to small areas where internet is not sufficient for them to use.

Steven Smith-Fleury

So, we’re quite flexible and we're...

Nadia Saleh

MS Teams.

Steven Smith-Fleury

We’re trying to work with what the manufacturers have?

Nadia Saleh

Correct.

Steven Smith-Fleury

In place already?

Nadia Saleh

Correct.

Steven Smith-Fleury

Terrific. That’s great.  I imagine it must be quite hard performing an inspection when you're not in the, the, the site, or on the site. What are some of the challenges with doing remote inspections?

Nadia Saleh

Inspecting remotely has been quite smooth for the most part. But as I'm sure you will understand, our key challenge in navigating through IT and internet issues to make sure all participants are present for all parts of the conversation.

Since we are also conducting inspections for overseas sites, we also have to manage time differences and working outside of the ordinary office hours. That means either very early in the morning or very late at night.

Steven Smith-Fleury

Nadia, can you tell us, is the remote inspection programme going to be ongoing?

Nadia Saleh

The move to remote inspections were driven purely by the need that arose from COVID-19 restrictions. Like anything, it comes with its pros and cons. But a decision hasn’t been yet made on whether TGA will maintain the remove inspection programme after COVID, restrictions are eased or lifted.

Steven Smith-Fleury

Is there somewhere, Nadia that manufacturers or sponsors can keep up to date on what's happening in this space?

Nadia Saleh

This would be discussed with the manufacturers when we contact them to inform them about the inspection. We would explain to them whether there is a change, it’s going to be onsite inspection or remote inspection.

Sometimes we have a hybrid of, if we have an inspector in that state, then, we will have remote and someone onsite at the same time. All these details will be explained to the manufacturers when we contact them to arrange for the inspection, to announce the inspection.

Steven Smith-Fleury

Wonderful. Now, Nadia, finally, have you got any tips for manufacturers who'll be going through the remote inspection process, anything to reduce anxiety around the process and help them to prepare?

Nadia Saleh

Of course. We do understand that any inspection can create some anxiety of manufacturers, and that’s no different from remote inspections. But TGA inspectors are highly experienced in conducting remote inspections and understand the challenges that come with them, especially after conducting a large number of remote inspections for national and, international sites.

We work closely with manufacturers from the time the inspection is announced by fully explaining the inspection process and discussing available technology resources that the manufacturers have to make the inspection process work smoothly. There is no need to be anxious about remote inspections. Our advice is the same as for regular inspections. Just be prepared, maintain open communication and work cooperatively with your inspectors, and the process will run nice and smooth.

Steven Smith-Fleury

That’s great. Thanks, Nadia. Now, if a manufacturer wants some more information on the process, on GMP, where, where should they go?

Nadia Saleh

TGA have sufficient information on its website to describe GMP requirements, licensing, certifications and inspections frequency matrices for the different products. In addition to that there is a GMP inbox. They can contact the TGA through the inbox, if they have any inquiry, and relevant staff will respond to their inquiries within short time.

Steven Smith-Fleury

Wonderful. Thanks, Nadia. And we'll put those contact details in today's show's show notes. So, Nadia, thank you so much for taking the time to speak with us today. I'm sure this helps clarify important information for manufacturers in relation to the inspection process, and also explains the work that TGA is doing to ensure that manufacturing inspections continue to take place in such unprecedented times. For more information on manufacturing, you can refer to the manufacturing therapeutic goods hub on our website.

To listeners, thank you for joining us today. In our next episode, we'll be discussing advertising therapeutic goods in Australia. So, please hit subscribe in the Podbean app or wherever you listen to your podcasts, and be sure to check out our website at www.tga.gov.au for more information on the regulation of therapeutic goods in Australia.