ZAS116 - Regulatory Challenges

Module 4 - How can I know that I’m getting it right?
Part I – Tools for Product Safety

Module Objectives

The objectives of this module are to:

  1. Get you thinking about the question “How can I know that I’m getting it right?”
  2. Introduce you to some of the tools that various applied science industries use to “get it right” in terms of product safety, and
  3. Outline what we’ll do in our Week 4 Tutorial.

How can I know that I’m getting it right?

In this, and the next two modules, our focus will shift from the stakeholders who care that your applied science business gets it right, to the tools that you can use to assist your business in getting it right. In this module our focus will be on getting it right in terms of product safety and, over the next couple of weeks, we’ll focus on getting it right in terms of environment protection and biosecurity, and the business practices inherent in product development, manufacture and commercialisation.

While the aquaculture, fermentation, and separation industries collectively facilitate the production of a vast array of consumer and industrial goods, in this module in particular our focus will be on foods/beverages and biopharmaceuticals, as it’s those products that tend to be of primary concern when it comes to product safety. That said, let’s get underway in looking at some of the tools that you could use to assist your business in getting it right...

P&P Activity – ‘Tools’ mind map

As you learn about specific tools that can be used to manage product safety, and listen to the experiences of various business owners, start building a mind map for yourself around the central question “How can I know that I’m getting it right?”, with your chosen type of enterprise in mind. Use the links in each section to skip to your industry of interest (i.e. aquaculture or fermentation and separation) to learn about industry-specific tools.

Systems, guidelines and SOPS

In seeking to “get it right” it’s important to be familiar with three broad groups of tools - systems, guidelines, and standard operating procedures (SOPs). We’ll begin with a brief definition of each before delving into more detail and/or providing you with some examples that are relevant to applied science businesses that produce foods (including seafoods) and beverages. You’ll then have an opportunity to look at some of the tools used to achieve product safety by those manufacturing biopharmaceuticals.

Systems are sets of detailed procedures, routines and documentation that comprise a plan to achieve a desired outcome, i.e. a high level of product safety.

SOPs are written, step by step procedures for carrying out a routine operation. An organisation can develop and use SOPs to ensure consistency in its processes and products/services, and to demonstrate regulatory compliance.

Guidelines provide advice that reflects current thinking on the way in which something should be carried out, interpreted, and/or responded to. They are often developed by regulatory authorities or industry bodies to assist businesses in achieving regulatory compliance.

Food (and beverage) safety management systems

The safety of foods, including aquaculture products and fermented foods and beverages, relates to their suitability for consumption. To be safe, a food should be ‘free’ from physical, biological, chemical and other hazards. In practice, a zero-tolerance approach to managing food safety risks is often not desirable and/or achievable, and thus the tools discussed below support business owners to provide an appropriate level of protection (ALOP) to the consumer.

A food safety management system (FSMS) is a key tool that can be used by business owners to assure the production of safe foods, and to demonstrate competence and compliance with legislative requirements, to customers and regulatory authorities alike. As you’ll see below, FSMSs come in various guises but most are based on:

  1. Properly established and implemented Prerequisite programs (PRPs), and
  2. The subsequent development and implementation of a Hazard Analysis and Critical Control Points (HACCP) plan.

Figure 1 – Key Elements of a Food Safety Management System

Figure 1 – Key Elements of a Food Safety Management System

Prerequisite Programs

Prerequisite programs (PRPs) address the practices and conditions that are essential to the production of safe products. They address facility and equipment design and construction, cleaning and sanitation, repair and maintenance, supplier control, personal hygiene, training, pest control, receiving, storage and shipping, traceability and recall, chemical control, and more. A business’ PRPs may include Good Agriculture Practices (GAPs), Good Aquaculture Practices (GAqPs), Good Hygiene Practices (GHPs), Good Manufacturing Practices (GMPs), Good Distribution Practices (GDPs), and/or Good Retail Practices, with those that are appropriate being determined by the nature of the business in question.

PRPs are often applied facility-wide (i.e. across processing and product lines) and their effective implementation is supported and demonstrated by way of the documentation of procedures (through SOPs) and the maintenance of records, respectively. PRPs provide an essential foundation for any FSMS. By implementing PRPs, a business can eliminate or manage many potential food safety hazards and, in doing so, simplify their HACCP plans substantially.

A little extra for those interested in aquaculture:

GAqPs have been defined as “… a series of considerations, procedures, and protocols designed to foster efficient and responsible aquaculture production and expansion and to help ensure final product quality, safety, and environmental sustainability” (Schwarz et al., 2019). In addition to the practices and conditions listed above, GAqPs should address issues such as fish health management, feeding practices, harvesting practices, and harvesting vessel design. If you’d like to learn more about GAqPs, take a look at this Overview of Good Aquaculture Practices.

A little extra for those interested in fermentation:

The Brewers Association of America’s website states that GMPs “… are the foundation of any quality or food safety program in any manufacturing setting”, that they “establish clear guidelines for the hygiene and cleanliness of the workers and their workplace”, and that “they dramatically decrease the food safety risk for customers”. GAPs and/or GDPs may also be appropriate if the business cultivates one or more of the primary products used in the manufacturing process or distributes its own products. If you’d like to learn a little more about GMPs, take a look at Good Manufacturing Practices set the Standard for Food Hygiene.

Hazard Analysis Critical Control Point

Once appropriate PRPs have been implemented, HACCP can be employed to manage specific foodborne hazards. HACCP can be applied to all parts of the production and supply chain from rearing/cultivating animals/plants through to retail. It was developed in the 1960s by NASA and a group of food safety specialists as means of ensuring the safety of food taken into space by astronauts, and today its seven principles (listed below) are used widely to guide business owners in the production of safe foods.

The seven principles of HACCP are:

  1. Conduct a hazard analysis
  2. Determine Critical Control Points (CCPs)
  3. Establish Critical Limits (CLs)
  4. Establish procedures to monitor control of CCPs
  5. Establish corrective actions to be undertaken when monitoring indicates that a particular CCP is not under control
  6. Establish verification procedures to confirm that the HACCP system is working effectively
  7. Establish a system of documentation for all procedures and record keeping

Take a look at the video HACCP – Making Food Products Safe, Part 1 to learn more about HACCP, the types of hazards it can be used to control, and the way in which it is used to make safe foods.

A little extra for those interested in aquaculture:

Watch a video looking at the importance of HACCP to Alaskan seafood processors, and another at its importance to British scallop processors. As you do this make some notes about the different hazards, and control measures used, in each case.

A little extra for those interested in fermentation:

Look at the Generic HACCP Application for the Production of Fruit Wine, Cider, Mead document and identify two biological and one chemical hazard relevant to these products, and the control measures recommended.

Food safety management standards and certification

As mentioned above, FSMSs come in many different guises. In the process of developing and implementing a FSMS a business may be guided by, or required to comply with, one or more food safety management standards. Food safety management standards (e.g. ISO 22000, the BRC Global Food Standard for Food Safety, FSSC 22000, and the Safe Quality Food Standard) that set out a series of requirements for FSMSs have been developed by numerous public and private entities. And while many businesses benefit from using such standards without seeking certification, businesses may wish, or be required, to seek third-party certification. By doing so, they demonstrate to customers and regulators alike that they have taken the steps necessary to assure product safety. Many standards require the implementation of procedures that go beyond the requirements of legislation. If you’d like to learn more about some of the well-known, widely used standards (ISO 22000, SQF and BRC) and the differences between them, you can read about them here.

Another term you’ll come across in this space is ‘code of practice’. The term ‘code’ is generally (although not always!) used to refer to a standard that has been adopted by one or more governmental bodies and is enforced by law, or that has been incorporated into a business contract (e.g. between a manufacturer and a retailer). The Food Standards Code (which is sometimes just referred to as ‘the code’) sets out a number of standards that are applicable to food manufactures in Australia, and addresses issues including food safety programs, practices and general requirements, labelling and information requirements, substances that may/may not be added to/present in foods, foods requiring pre-market clearance, and more. The Food Standards Code is enforced by the individual states and territories of Australia.

A little extra for those interested in aquaculture:

In Tasmania, a number of the seafood industry sectors and the state government are cooperatively developing FSMSs to assist businesses to ‘get it right’. The FSMS for Live Tasmanian Farmed Bivalve Molluscs provides an example. Have a quick look through it now and take note of the specified PRPs.

A little extra for those interested in fermentation:

In Australia, a number of industry sectors and state government departments are developing FSMSs to assist businesses to ‘get it right’. The Uncooked Comminuted Fermented Meats (UCFM) Manufacturer Food Safety Plan provides an example. Have a quick look through it now and take note of the specified PRPs.

A note on Food Safety Objectives

As indicated at the beginning of this module, it is often unnecessary and/or impractical to adopt a zero-tolerance approach to managing food safety risks. Rather, business owners should provide an appropriate level of protection (ALOP) to the consumer. But what is an appropriate level of protection and how can business owners know they are achieving it?

Well, the answer to the first question is a matter for policy makers who, under the Sanitary and Phytosanitary Measures Agreement, are entitled to maintain a level of protection they consider appropriate to protect life or health within their territories. Governments in a number of countries are now undertaking quantitative risk assessments in which risk is assessed as a function of the likelihood of exposure and the severity of a given hazard. A Food Safety Objective (FSO) translates an acceptable degree of risk (another term for ALOP) into a definable goal - a specified maximum frequency and/or concentration of a hazard in a food at the time of consumption that is considered safe or meets the level of protection demanded (ICMSF, 2005). FSOs can be further translated into practical targets for industry. So-called performance objectives (POs) define the level or frequency of contamination that industry must aim for at the point of production, so as to ensure that a FSO is consistently met. Business owners retain flexibility, however, in terms of the strategies and technologies that they use to meet the objectives.

Standard Operating Procedures

OPs are written, step by step procedures for carrying out routine operations. They can be applied in all areas of a business to ensure consistency in processes and products/services, and to demonstrate regulatory compliance. They are an essential element of food safety management systems and, as you’ll see in next week’s module, environmental management systems. In his article entitled ‘SOPs: least understood, most important tool to ensure regulatory compliance’, Mukesh Kumar (2011) points out that “although most organisations appreciate the importance of SOPs, they may have a poor understanding of many aspects of SOP creation, maintenance, training and organisation …”. Kumar presents the following as a list of best practices for SOP creation.

  • Make them task specific
  • Include a sufficient level of detail (i.e. step-by-step instructions)
  • Use “plain” language which is easily understood
  • Define responsible personnel by their position or job title, not name
  • Annotate them appropriately with version numbers, effective dates, and categorisation
  • Update the relevant SOP whenever a process changes
  • Make them accessible to relevant personnel - note that not all employees need access to all SOPs
  • Establish documentation (checklists, sign-off sheets, etc) that can be used to demonstrate conformance

If you’d like to learn more about writing SOPs and/or check out a couple of good examples, take a look at this SOP Fact Sheet.

Guidelines for product safety

Choose your industry of interest, aquaculture or fermentation and separation.

Guidelines for aquaculture

Various guidelines have been developed, primarily by regulatory and industry bodies, to assist business owners ‘get it right’ in terms of food safety. Below is a list of some of the many guidelines that are available globally to assist businesses within the aquaculture industry. If you’d like to know more about any of these guidelines for product safety in aquaculture you can follow the links provided.

Guidelines for fermentation

Various guidelines have been developed, primarily by regulatory and industry bodies, to assist business owners ‘get it right’ in terms of food safety. Below is a list of some of the many guidelines that are available to assist businesses operating within the fermented food/drinks industry. If you’d like to know more about any of these guidelines you can follow the links provided.

Future Industry: How can I know that I’m getting it right for biopharmaceuticals?

Biopharmaceuticals are growing business, including in industry sectors you might not already have thought of! For just a taste, take a look at:

In 2016 the global biopharmaceutical contract manufacturing and research market size was estimated at 18,000,000,000 US dollars. And with big growth comes big opportunity. So even if you’ve never thought of it before, this could be the future of your employment or even your very own business.

SAFE BIOPHARMACEUTICALS

The safety of a biopharmaceutical must be assured in terms of:

  1. the effect(s) of the active ingredient(s)/carriers on human health (biopharmaceutic safety),
  2. freedom from chemical, biological or physical hazards, and
  3. the consistent delivery of an appropriate quantity of the active ingredient(s).

So, ‘getting it right’ with biopharmaceuticals begins long before the point of commercial manufacture. If you’d like to learn about some of the tools used to assure the above, read on.

TOOLS TOWARDS SAFE BIOPHARMACEUTICALS

In Module 3 we noted that, in Australia, all medicines must be registered or listed on the Australian Register of Therapeutic Goods (ARTG) before being supplied. We also indicated that to have a medicine entered in the ARTG, a sponsoring company must lodge an application that includes data demonstrating biopharmaceutic safety of the product or justification for not providing such data. That data is typically collected through preclinical and clinical trials. The Australian Government’s Therapeutic Goods Administration (TGA) have published the ‘Australian clinical trial handbook’ to help sponsoring companies ‘get it right’ when collecting the data they require to demonstrate the biopharmaceutic safety of a new medicine.

Companies manufacturing biopharmaceuticals, either for clinical trials or for supply to the public, have a responsibility to produce them in a manner that ensures freedom from chemical, biological and physical hazards, as well as accuracy and consistency with regards to the prescribed quantity of the active ingredient supplied in each unit. To that end, manufacturers of biopharmaceuticals are required to employ GMPs. As pointed out above in relation to the manufacture of safe foods, GMPs are the foundation of any quality program in a manufacturing setting. And in the biopharmaceutical industry, quality is synonymous with safety.

In Australia the Therapeutic Goods (Manufacturing Principles) Determination 2018 specifies that medicines supplied in Australia have to meet the Pharmaceutical Inspection Convention and Pharmaceutical Co-operation Scheme (jointly known as PIC/S) Guide to Good Manufacturing Practice – 01 January 2017, PE009-13. PIC/S develop international standards for the purposes of harmonisation and cooperation in the field of GMP as it applies to the pharmaceutical industry. You can take a look at the PIC/S Guide to GMP here if you like. Part 1 of the guide covers GMP principles for the manufacture of medicinal products, and Part 2 covers GMP principles for the manufacture of active substances used as starting materials.

In addition to GMPs, other tools for quality assurance may be employed by biopharmaceutical manufacturers to assure product safety. These include Continued Process Verification (CPV) - a system designed to provide ongoing assurance that the manufacturing process remains in a state of control, and Process Analytical Technology (PAT) – defined by the USFDA as “a mechanism to design, analyse, and control pharmaceutical manufacturing processes though the measurement of Critical Process Parameters (CPP) which affect Critical Quality Attributes (CQA)”. Its purpose is to ensure product quality through enhanced understanding and control of the manufacturing process, with the latter being achieved through the timely (preferably in-line or on-line) monitoring of CPPs.

CPV and PAT can also be employed as part of a broader strategy for ensuring the quality/safety of biopharmaceuticals known as Quality by Design (QbD). The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines Q8 (R2) defines QbD as “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding, based on sound science and quality risk management”. It’s underpinned by the idea that quality/safety should be ‘built into a product’. Parker Hannifin, a fortune 250 global leader in motion and control technologies explains that QbD is a “… method by which the critical quality attributes (QCAs) of a biologic product are identified and an appropriate manufacturing process is defined … by performing small-scale, often multi-factorial experiments and using a risk-based approach to quality. The knowledge obtained can be used to generate a design space for manufacturing, which will ensure consistent product quality if the process is operated within the design parameters”.

If you’d like to know more about the use of CPV, PAT and QbD in the biopharmaceutical industry, take a look at the following guidelines.

What we’ll do in Tutorial 4

In our Week 4 Tutorial we’ll put what we’ve learnt so far into perspective by listening to, and reflecting on, some interviews with professionals from the aquaculture, food and pharmaceutical/separation industries in which they describe their regulatory environments and some of the challenges they face on a day-to-day basis in navigating those environments.

See you there!

Unit Glossary

The unit glossary will be updated with new terms as our unit progresses, making it an excellent resource to refer to each week. Below are the new terms from this week's content, they've also been added to the full Unit Glossary, which you can view here.

Appropriate Level of Protection (ALOP) – an acceptably low level of risk considered suitable, by a country’s policy makers, to protect life or health

Biopharmaceuticals – medicines manufactured in, extracted from, or made semi-synthetically from biological sources

Clinical trials – studies that evaluate the effects of medicines or medical devices on the health outcomes of humans

Code of practice – a standard that has been adopted by one or more governmental bodies and is enforced by law, or that has been incorporated into a business contract

CODEX – the acronym for Codex Alimentarius Commission, an organisation established by the United Nation’s Food and Agriculture Organisation and the World Health Organisation, that develops international food standards, guidelines and codes of practice

Continued Process Verification (CPV) – the collection and statistical analysis of bioprocessing data used to ensure that a product remains within pre-determined quality limits

Critical Control Points (CCPs) – a point at which control can be applied and is essential to prevent or eliminate a food safety hazard or reduce it to an acceptable level

Critical Limits (CLs) – a maximum and/or minimum value to which a biological, chemical or physical parameter must be controlled at a CCP to prevent, eliminate or reduce to an acceptable level the occurrence of a food safety hazard

Food Safety Management Standards – set out a series of requirements for food safety management systems that are designed to assure the production of safe food and regulatory compliance

Food Safety Management System (FSMS) – a systems-based approach to controlling food safety hazards

Food Safety Objectives (FSOs) - a specified maximum frequency and/or concentration of a hazard in a food at the time of consumption that meets the level of protection demanded

Good Aquaculture Practices (GAqPs) – a series of practices that help ensure product quality, safety, and environmental sustainability

Good Manufacturing Practices (GMPs) – a series of practices that help ensure that manufactured goods are consistently produced and controlled according to quality standards

Guidelines – advice that reflects current thinking on the way in which something should be carried out, interpreted, and/or responded to; compliance with guidelines is not mandatory

Hazard – a potential source of harm

Hazard Analysis – the process of collecting and evaluating information on hazards associated with a product to identify their significance

Hazard Analysis Critical Control Points (HACCP) – a proactive, systematic approach to controlling foodborne hazards that identifies hazards and establishes controls that will prevent, eliminate or reduce hazards to an acceptable level; pronounced has-sup

International Organisation for Standardisation (ISO) – an international organisation that brings together representatives from various national standards organisations to develop international standards

ISO 22000 – A standard developed by ISO that sets out the requirements for a food safety management system that would enable a company to comply with food safety regulations all over the world

Performance Objectives (POs) – a specified maximum frequency and/or concentration of a hazard in a food at a particular point in the food chain that should not be exceeded in order to achieve the food safety objective

Prerequisite programs – series of measures or activities that address the basic conditions and operating procedures that are essential for the production of safe foods; instituted to prevent common hazards from occurring

Process Analytical Technology (PAT) – a system designed to reduce process variability and, thereby, product variability that integrates on-line measurement and/or modelling of critical process parameters and/or critical quality attributes of in-process materials with automated feedback control of the processing parameters

Quality by Design (QbD) – a systematic approach to development that seeks to ‘build quality in’, beginning with pre-defined objectives, and emphasizing product and process understanding, and process control

Quantitative risk assessment – the use of measurable, objective data to understand the risks associated with potential hazards

Risk – the potential of losing of something of value (e.g. health, life) by exposure to a hazard

Standard Operating Procedures (SOPs) – written step by step procedures for carrying out a routine operation that ensure consistency in an organisation’s processes and products/services

Systems – sets of detailed methods, procedures, routines and documentation that comprise a plan to achieve a desired outcome e.g. the production of a safe product

Zero-tolerance – non-acceptance of any degree of risk