Author: Jeremiah Genest

Quality professional with over 20 years of experience. Gamer and storyteller with forty years of practice.

ISO 8061 Adoption in Pharma

How widespread is adoption of ISO 8601, the standard for date and time formats? Is your company aligned?

I see ISO 8601 widely used in scientific fields, software development, and more and more international correspondence. Yet, I think its fair to say the adoption in pharma has been lacking. So I am really curious, has your organization fully or partially adopted it? If so, how did it go?

Date Format

The basic principle of ISO 8601 for dates is to represent them in a descending order of significance:

  • Complete date: YYYY-MM-DD (extended format) or YYYYMMDD (basic format)
    Example: 2022-09-27 or 20220927
  • Year and month: YYYY-MM
    Example: 2022-09
  • Year only: YYYY
    Example: 2022

Time Format

ISO 8601 defines the following time format:

  • Basic format: Thhmmss
  • Extended format: Thh:mm:ss

Where:

  • T is the time designator
  • hh represents hours (00-24)
  • mm represents minutes (00-59)
  • ss represents seconds (00-60, where 60 is used for leap seconds)

Example: T134730 or T13:47:30 represents 1:47:30 PM

Combined Date and Time

ISO 8601 allows combining date and time representations:

  • YYYY-MM-DDThh:mm:ss or YYYYMMDDThhmmss

Example: 2022-09-26T07:58:30 represents September 26, 2022, at 7:58:30 AM

Time Zone Designators

The standard also specifies how to represent time zones:

  • Z: Represents UTC (Coordinated Universal Time)
  • ±hh:mm or ±hhmm: Represents the offset from UTC

Example: 2022-09-07T15:50+00:00 or 2022-09-07T15:50Z represents 3:50 PM UTC on September 7, 2022.

Key Features

  1. The standard uses the Gregorian calendar.
  2. It employs a 24-hour clock system.
  3. All elements are represented by a fixed number of digits, zero-padded if necessary.
  4. The standard allows for reduced precision by omitting certain elements.
  5. It can represent dates, times, time intervals, and recurring time intervals

Government and Official Use

Many countries have officially adopted ISO 8601 as their recommended or mandated date format for government and official use. For example:

  • The UK government has mandated the use of ISO 8601 for IT systems, APIs, and machine-to-machine communication.
  • Canada’s government and Standards Council officially recommend ISO 8601 for all-numeric dates.
  • Australia recommends ISO 8601 as the short date format for government publications.

The European Union has adopted ISO 8601 as the European Standard EN 28601, making it valid in all EU countries.

Has anyone seen Health Canada or an EMA (and/or national competent authority) push back at a time/date not in ISO 8061 format? I think there has been a lot of push back in health care around adoption, for example the NHS in the UK uses 01-JAN-2017 for medicine labels even though the UK has adopted ISO 8061.

I find it fascinating that the eCTD specification does not mandate a specific date format for metadata or content within submissions, allowing flexibility for regional requirements. Yet we have seen many health authorities that have implemented eCTD do recommend or require the use of ISO 8601 date formats in certain contexts:

  • The US FDA guidance on eCTD recommends using ISO 8601 format (YYYY-MM-DD) for dates in the submission.
  • The EU guidance on eCTD also recommends ISO 8601 format for dates in certain metadata fields.

The eCTD XML backbone uses the W3C XML Schema date and dateTime datatypes, which are based on ISO 8601 formats. While not explicitly requiring ISO 8601, the eCTD specification does emphasize the importance of consistent and unambiguous date representations, which aligns with the goals of ISO 8601. It really makes me wonder when this decision will start rippling through other parts of the industry.

I’d love your thoughts.

Preparing your BCP for Trump’s Attacks on Immigration

Time (maybe past-time) to evaluate your organization’s business continuity plan and anticipate the potential actions against immigrants, in particular the potential impact of Trump’s proposed immigration policies on the facility cleaning industry, particularly cleanrooms, which could be significant.

Labor Shortage

The cleaning industry, including cleanroom maintenance, heavily relies on immigrant labor. A mass deportation policy could lead to:

  • Significant workforce reduction: Many cleaning companies employ immigrant workers, both documented and undocumented. A large-scale deportation could severely reduce the available workforce.
  • Increased labor costs: With fewer workers available, companies may need to offer higher wages to attract and retain employees, potentially increasing operational costs.

Industry Disruption

The cleanroom industry, which requires specialized skills and training, could face particular challenges:

  • Loss of experienced workers: Cleanroom maintenance requires specific knowledge and expertise. Deporting experienced workers could lead to a skills gap in the industry.
  • Reduced productivity: As companies struggle to replace deported workers, there might be a temporary decrease in productivity and quality.
  • Increased costs for clients: Higher labor costs in the cleaning industry could be passed on to clients, potentially affecting industries that rely on cleanroom facilities, such as pharmaceuticals and electronics manufacturing.

Actions to Evaluate

Time to evaluate internal training programs to quickly upskill current and new workers, particularly for specialized cleanroom maintenance. Be prepared for the need to have your staff step in and clean, on the moment’s notice. This is a key action to have in the business continuity plan, and frankly should already be there.

Compliance and Legal Challenges

Beyond that, companies should be evaluating their other plans with broad stakeholders like HR and legal for when law enforcement comes calling as a result of heightened enforcement and audits of cleaning companies to ensure compliance with immigration laws. Remember these cleaners work side-by-side with your staff and quite frankly, are really hard to tell the difference. Are you prepared to side with law enforcement, or delay law enforcement? What is your risk tolerance for navigating the complex legal situations, particularly if long-term employees are suddenly subject to deportation?

While the full extent of the impact remains uncertain, Trump’s proposed immigration policies could significantly disrupt the facility cleaning industry, which will greatly impact every manufacturing site I know. The industry may need to adapt quickly to potential labor shortages, increased costs, and changing regulatory landscapes, while navigating the thorny ethical considerations.

No time like the present to start.

What is Ahead for US Pharma?

It has been a wild ride this past week. I know my family and I have been on an emotional rollercoaster, and I bet many of you are feeling the same way. One question that keeps popping up in our household (and probably yours too) is: “What does this mean for my job, and should I be freaking out?”

Short-term outlook: Keep calm and carry on

First things first, take a deep breath. In the immediate future, it’s unlikely that we’ll see any massive shifts in pharma world. Most of us can probably continue our daily grind without too much disruption. So, for now, it’s business as usual, folks! Unfortunately that business has been pretty tough the last two years.

Long-term forecast: Cloudy with a chance of uncertainty

Now, here’s where things get a bit murky. The long-term outlook? Well, it’s like trying to predict the weather a year from now – pretty darn tricky. What we do know is that this situation has cranked up the uncertainty dial, and let’s face it, uncertainty in the pharmaceutical world is very unwelcome.

We already have a hefty dose of uncertainty due to the 2024 Supreme Court decisions, which are slowly starting to have impact but the boundaries are really unknown. Add to that an incoming administration with a noted dislike (and a set of vendettas) against the HHS and FDA, and government employees. And on top of that we have the wild card of Robert F. Kennedy Jr. being able to “go wild on health” – whatever that ends up meaning but my fear is nothing good.

But I also need to be pragmatic, and as a quality individual involved in risk management and managing uncertainty, I need to start evaluating impacts. Here are the things I am looking at.

On-Shoring

On-Shoring has been a growing conversation for years. We are an incredibly global industry and have been hard hit by a variety of supply disruptions:

  1. Global Pandemic: COVID-19 threw a massive wrench into our well-oiled supply chain machine.
  2. Geopolitical Tensions: The ongoing trade tiffs between major economies have kept us on our toes.
  3. Natural Disasters: Mother Nature hasn’t exactly been playing nice lately.
  4. Labor Shortages: Finding skilled workers has become a bit like searching for a needle in a haystack.

Add to this cocktail the ongoing GMP issues with sites in key manufacturing countries like India and China, and you’ve got a recipe for some serious supply chain headache,

Add to that we have a whole lot of talk of tariffs. The incoming Trump administration is practically drooling to raise tariffs which will have some serious implications:

  • Market Access Issues: Suddenly, selling your products in certain countries becomes a whole lot trickier.
  • Higher Costs: Tariffs often mean higher prices for imported goods.
  • Retaliation Risks: When one country imposes tariffs, others tend to follow suit.

The Critical Component Conundrum

Here’s where things get scary. We are seeing an increase in both price and availability issues for critical raw materials and components. And it is not just about overseas suppliers – even our domestic suppliers are feeling the heat. Remember the great plastics shortage that hit our Single-Use System (SUS) component suppliers? That is potentially just the tip of the iceberg.

The Ripple Effect

Now, let’s connect the dots:

  1. Supply Chain Vulnerability: Our global supply chains are showing their weak spots.
  2. Critical Item Shortages: There’s a growing concern about shortages of essential items.
  3. Price Hikes: As supplies tighten and tariffs kick in, prices are heading north.
  4. Market Access Challenges: A potential trade war could make it tough to serve international markets from the U.S. And remember, we are a very global industry.

Risk Management Approach

  1. Diversify Supply Sources: Don’t put all your eggs in one basket (or country).
  2. Build Resilience: Create buffer stocks of critical components.
  3. Explore On-Shoring Options: Look into bringing some production closer to home.
  4. Stay Flexible: Be ready to pivot your strategy as the global situation evolves.
  5. Plan for multi-country impact: Evaluate what happens when other countries start retaliating and it becomes difficult to get clinical or commercial supply into a country.

Regulatory Changes

Here are my fears where RFK Jr can really do damage. He may push for less stringent approval processes for certain drugs or treatments he favors, potentially allowing more alternative or “natural” products to enter the market. Conversely, he could impose stricter regulations on vaccines and other pharmaceutical products he views skeptically (which is all of them).

There may be efforts to roll back regulatory controls that currently protect public health, potentially allowing unproven treatments to reach consumers more easily. All of this uncertainty is going to be difficult and will impact company’s ability to raise funds. Which will impact the job market. And it has been a bad couple of years for layoffs.

Best Practices for Managing the Life-Cycle of Single-Use Systems

Single-use systems (SUS) have become increasingly prevalent in biopharmaceutical manufacturing due to their flexibility, reduced contamination risk, and cost-effectiveness. The thing is, management of the life-cycle of single-use systems becomes critical and is an area organizations can truly screw up by cutting corners. To do it right requires careful collaboration between all stakeholders in the supply chain, from raw material suppliers to end users.

Design and Development

Apply Quality by Design (QbD) principles from the outset by focusing on process understanding and the design space to create controlled and consistent manufacturing processes that result in high-quality, efficacious products. This approach should be applied to SUS design.

ASTM E3051 “Standard guide for specification, design, verification, and application of SUS in pharmaceutical and biopharmaceutical manufacturing” provides an excellent framework for the design process.

Make sure to conduct thorough risk assessments, considering potential failure modes and effects throughout the SUS life-cycle.

Engage end-users early to understand their specific requirements and process constraints. A real mistake in organizations is not involving the end-users early enough. From the molecule steward to manufacturing these users are critical.

    Raw Material and Component Selection

    Carefully evaluate and qualify raw materials and components. Work closely with suppliers to understand material properties, extractables/leachables profiles, and manufacturing processes.

    Develop comprehensive specifications for critical materials and components. ASTM E3244 is handy place to look for guidance on raw material qualification for SUS.

    Manage the Supplier through Manufacturing and Assembly

    Implementing robust supplier qualification and auditing programs and establish change control agreements with suppliers to be notified of any changes that could impact SUS performance or quality. It is important the supplier have a robust quality management system and that they apply Good Manufacturing Practices (GMP) through their facilities. Ensure they have in place appropriate controls to

    • Validate sterilization processes
    • Conduct routine bioburden and endotoxin testing
    • Design packaging to protect SUS during transportation and storage. Shipping methods need to protect against physical damage and temperature excursions
    • Establish appropriate storage conditions and shelf-life based on stability studies
    • Provide appropriate labeling and traceability
    • Have appropriate inventory controls. Ideally select suppliers who understand the importance of working with you for collaborative planning, forecasting and replenishment (CPFR)

    Testing and Qualification

    Develop a comprehensive testing strategy, including integrity testing and conduct extractables and leachables studies following industry guidelines. Evaluate the suppliers shipping and transportation studies to evaluate SUS robustness and determine if you need additional studies.

      Implementation and Use

      End users should have appropriate and comprehensive documentation and training to end users on proper handling, installation, and use of SUS. These procedures should include how to perform pre-use integrity testing at the point of use as well as how to perform thorough in-process and final inspections.

      Consider implementing automated visual inspection systems and other appropriate monitoring.

      Implement appropriate environmental monitoring programs in SUS manufacturing areas. While the dream of manufacturing outdoors is a good one, chances are we aren’t even close yet. Don’t short this layer of control.

        Continuous Improvement

        Ensure you have appropriate mechanisms in place to gather data on SUS performance and any issues encountered during use. Share relevant information across the supply chain to drive improvements.

        Conduct periodic audits of suppliers and manufacturing facilities.

        Stay updated on evolving regulatory guidance and industry best practices. There is still a lot changing in this space.